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Ochoa was a biochemist and molecular biologist whose research was devoted to understanding enzymes and their role in intermediary metabolism. He was one of the first scientists to show the pivotal role of high energy phosphates, like adenosine triphosphate, in the storage and release of energy. During this work he discovered the enzyme polynucleotide phosphorylase, which plays an important role in the synthesis of ribonucleic acid (RNA). This enzyme provided the foundation for the subsequent synthesis of artificial RNA and the breaking of the human genetic code. Ochoa was awarded the Nobel Prize for Medicine in 1959 for his work on the biological synthesis of RNA.1905-09-24T00:00:00+0000| 24 Sep 1905 | | Severo Ochoa was born in Luarca, SpainOchoa | New York University |
Pirie was a virus physiologist and biochemist. He helped determine that the genetic component of viruses is RNA. Before this viruses were thought to be made up completely of proteins. During World War II he explored the possibility of extracting edible proteins from leaves, research that he carried on into the 1970s. His experiments were directed towards solving the food problem posed by the growing world population. He hoped to replace the inefficient method of feeding animals to secure protein for the diet.1907-07-01T00:00:00+0000| 1 Jul 1907 | | Norman Wingate (Bill) Pirie was born in Eastbourne, UKPirie | Rothamsted Experimental Station |
Stein was a biochemist who shared the 1972 Nobel Prize for contributing to understanding the composition and functioning of ribonuclease, an enzyme that catalyses the break down of RNA into smaller components. It was the first structure and sequence worked out for any enzyme. Stein carried out the work with his colleague Stanford Moore in 1963. The two scientists were aided by their invention of the first means for automated amino acid analysis. In addition to his work on ribonuclease, Stein showed how proteins that are comprised of the same amino acids can have very different characteristics and functions. 1911-06-25T00:00:00+0000| 25 Jun 1911 | | William H Stein was born in New York NY, USAStein | Rockefeller University |
Zamecnik pioneered the in vitro synthesis of proteins and helped determine the way cells generate proteins. Together with Mahlon Hoagland and Mary Stephenson he showed that protein synthesis was activated by adenosine 5'-triphosphate and that ribosomes were the site of protein assembly. He also subsequently helped to discover transfer RNA and is credited with laying the foundation for the development of antisense therapies, a type of gene therapy. 1912-11-22T00:00:00+0000| 22 Nov 1912 | | Paul Zamecnik was born in Cleveland, Ohio, USAZamecnik | Massachusetts General Hospital |
Anfinsen was a biochemist who spent his career studying the relationships between structure and function in proteins. He is best known for his studies of ribonuclease, a type of nuclease that catalyses the degradation of RNA into smaller components. In 1972 he was awarded the Nobel Prize for Chemistry for his work 'on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation.' 1916-03-26T00:00:00+0000| 26 Mar 1916 | | Christian B Anfinsen was born in Monessen, Pennsylvania, USA Anfinsen | National Institutes of Health |
Kornberg was a biochemist renowned for his research on enzymes which create DNA. In 1956 he and his team isolated the first enzyme known to be involved in the replication of DNA. It would be called DNA polymerase I. For this work Kornberg shared the 1959 Nobel Prize for Medicine. The Prize was given for the discovery of the 'mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.'1918-03-03T00:00:00+0000| 3 Mar 1918 | | Arthur Kornberg was born in Brooklyn NY, USAKornberg | Stanford University |
Monod was a biochemist who, together with Francois Jacob, worked out the genetic control of enzyme and virus synthesis based on their experiments with Escherichia coli in the early 1960s. They proposed that a messenger molecule in cells carries codes from the DNA in the cell nucleus to the site of protein synthesis in the cell's cytoplasm. This molecule was later called messenger RNA which is now the basis of COVID-19 vaccines. Based on his work Monrod was awarded a Nobel Prize for Medicine in 1965.
1920-06-07T00:00:00+0000| 7 Jun 1920 | | Jacques Monod was born in Nancy, FranceMonod | Pasteur Institute |
Holley was a biochemist who shared the 1968 Nobel Prize for Medicine for explaining how the genetic code controls the synthesis of proteins. This stemmed from his research on RNA which he began in the late 1940s. By 1960 and he and collaborators showed that amino acids were assembled into proteins by transfer RNAs (tRNAs). In 1965 he managed to determine the composition of a tRNA that incorporates the amino acid alanine into protein molecules. 1922-01-28T00:00:00+0000| 28 Jan 1922 | | Robert W Holley was born in Urbana IL, USAHolley | Cornell University |
A molecular biologist, Smith was a key pioneer in nucleic acid research. One of the few to realise the importance of nucleic acids before Watson and Crick uncovered the structure of DNA in 1953, Smith helped to elucidate the structure of ribonucleic acid molecules (RNA), the genetic material of many plant and animal viruses. This was helped by his development of paper chromatographic methods for analysing nucleosides and other units which make up DNA. He also helped to discover rare and unexpected modifications of DNA bases in bacterial genomes which are now understood to prevent attack from DNA viruses. 1924-12-08T00:00:00+0000| 8 Dec 1924 | | John D Smith was born in Southampton, UKJohn D Smith | California Institute of Technology, Laboratory of Molecular Biology |
A chemist and biophysicist, Klug won the 1982 Nobel Prize in Chemistry for the development of crystallographic electron microscopy. He used the technique to investigate nucleic acid-protein complexes and the structure of viruses. He developed an interest in viruses after meeting Rosalind Franklin in late 1953. Klug also discovered zinc-finger proteins, a class of proteins that bind specific DNA sequences. Scientists now use the modular nature of these proteins to design synthetic proteins for targeted therapies. Klug went to South Africa with his Jewish parents when he was two and then settled in England after completing his master's degree. Klug was the director of the Laboratory of Molecular Biology (1986-1996) and President of the Royal Society (1995-2000). 1926-08-11T00:00:00+0000| 11 Aug 1926 | | Aaron Klug was born in Zelvas, LithuaniaKlug | Laboratory of Molecular Biology |
Gilbert is a molecular biologist. He was involved in some of the early efforts to pioneer techniques for determining base sequences in nucleic acids, known known as DNA sequencing, for which he shared the Nobel Prize for Chemistry in 1980. He was the first scientist to propose the existence of intron and exons. In 1986 Gilbert became a proponent of the theory that the first forms of life evolved out of replicating RNA molecules. The same year he began campaigning to set up the Human Genome Project. He was also a co-founder and the first Chief Executive Officer of Biogen, a biotechnology company originally set up to commercialise genetic engineering.1932-03-21T00:00:00+0000| 21 Mar 1932 | | Walter Gilbert was born in Boston MA, USAGilbert | Harvard University, Biogen |
Altman was a molecular biologist who shared the 1989 Nobel Prize for Chemistry for discovering the catalytic properties of RNA. This emerged out of some work Altman carried out between 1978 and 1983 on a bacterial enzyme called RNAs-P. His research helped transform the basic understanding of nuclear acids, which up to this moment had been understood to only carry genetic information. It also opened up the possibility of using genetic engineering to develop new forms of therapy against viral infections. 1939-05-07T00:00:00+0000| 7 May 1939 | | Sidney Altman was born in Montreal, CanadaAltman | Harvard University, Laboratory of Molecular Biology, Yale University |
Yonath is a biochemist who won the Nobel Prize for Chemistry in 2009 for helping to map the structure of ribosomes, the molecule that helps translate RNA into protein. She started the research in the 1970s using x-ray crystallography. By 2001 she had worked out the complete high-resolution of structures of both ribosomal subunits and discovered a region important to the process of polypeptide polymerisation. In addition to this work Yonath had elucidated the modes of action of over 20 different antibiotics that target the ribosome, which has provided insights into the mechanisms of drug resistance and antibiotic sensitivity. 1939-06-22T00:00:00+0000| 22 Jun 1939 | | Ada E Yonath was born in Jerusalem, Palestine (now Israel)Yonath | Weizmann Institute |
Steitz is a biochemist and biophysicist who shared the 2009 Nobel Prize for Chemistry for elucidating the atomic structure and function of ribosomes, tiny particles made up of RNA and proteins involved in protein synthesis. He and colleagues determined this in 2000 using x-ray crystallography. The work opened up a new pathway to the discovery and development of new classes of antibiotics. 1940-08-23T00:00:00+0000| 23 Aug 1940 | | Thomas A Steitz was born in Milwaukee, WI, USASteitz | Yale University |
Sharp is a geneticist and molecular biologist. He shared the 1993 Nobel Prize for Medicine for the discovery of RNA splicing. This was awarded on the back of some research he did in 1977 which showed that RNA can be divided up into introns and exons, after which the exons can be joined together. This process can happen in different ways. It provides the means for the gene to form a number of different proteins. Sharp also co-founded Biogen, set up in 1978, and helped found Alnylam Pharmaceuticals and Magen Biosciences.1944-06-06T00:00:00+0000| 6 Jun 1944 | | Phillip A Sharp was born in Falmouth, Kentucky, USASharp | Massachusetts Institute of Technology, Biogen, Alynylam Pharmaceuticals, Magen Biosciences |
Kornberg is a biochemist whose research is focused on working out the mechanism and regulation of transcription, which is the first step in the pathway of gene expression. In 2006 he won the Nobel Prize for working out the protein pathway that a cell's genetic information takes when transferred to a new cell. He showed how information is carried from the genes and converted to molecules called messenger ribonucleic acid (RNA). This he worked out by mapping out the process in yeast. Kornberg was the first to work out how transcription works at a molecular level in eukaryotes, a group of organisms, including humans, whose cells have a well-defined nucleus. 1947-04-24T00:00:00+0000| 24 Apr 1947 | | Roger D Kornberg was born in St. Louis, MO, USAKornberg | Stanford University |
Cech is a chemist who shared the 1989 Nobel Prize for Chemistry for the discovery of the catalytic properties of RNA. This was based on his investigation of splicing RNA in Tetrahymena thermophila, a unicellular organism, during the 1970s. He discovered that unprocessed RNA molecules could splice themselves and showed that RNA molecules are not restricted to being passive carriers of genetic information. 1947-12-08T00:00:00+0000| 8 Dec 1947 | | Thomas R Cech was born in Chicago IL, USACech | University of Colorado |
Ribonuclease is a small protein that helps to break down RNA. It was one of the first proteins to be separated with column chromatography. The work was published in AJP Martin, RR Porter (July 1951), ‘The chromatographic fractionation of ribonuclease’, The Biochemical Journal, 49/2, 215-8.1951-07-01T00:00:00+0000| July 1951 | | Ribonulcease separated into two homogenous forms using column chromatographyPorter, Martin | National Institute for Medical Research |
Szotak is a biologist who was awarded the Nobel Prize for Physiology or Medicine for helping to discover how chromosomes are protected by telomeres, a section of DNA at the end of a chromosome. He is also known for having constructed the world's first yeast artificial chromosome, a breakthrough that has helped scientists to map the location of genes in mammals and develop techniques for mapping genes. Szotak is also responsible for the development of a technique known as in vitro evolution of RNA which makes it possible to discover RNAs with desired functions. 1952-11-09T00:00:00+0000| 9 Nov 1952 | | Jack Szostak was born in London, United KingdomSzotak | Harvard University |
The discovery was made by Paul C. Zamecnik with his colleagues Mahlon Hoagland and Mary Stephenson. tRNA is essential to protein synthesis. The molecule helps shuttle amino acids to the ribosome, the cell's protein factory. The work was subsequently published in MB Hoagland, ML Stephenson, JF Scott, ML Stephenson, LI Hecht, PC Zamecnik, 'A soluble ribonucleic acid intermediate in protein synthesis', Journal Biological Chemistry, 231 (1958), 241-57. 1956-01-01T00:00:00+0000| 1956 | | Transfer RNA (tRNA) discoveredZamecnik, Hoagland, Stephenson, | Harvard University |
The molecule was first observed by the American scientists Elliot Volkin and Lazarus Astrachan in experiments conducted with bacteriophage-infected Escherichia coli. Calling the new molecule 'DNA-like RNA', Volkin and Astrachan published their finding in 'Phosphorus incorporation in Escherichia coli ribonucleic acid after infection with bacteriophage T2', Virology, 2 (1956), 149-61. 1956-01-17T00:00:00+0000| 1956 | | First observation of messenger RNA, or mRNAAstrachan, Volkin | Oak Ridge National Laboratory |
Fire is a biologist, pathologist and geneticist. In 1998 he and other colleagues working at Carnegie Institute reported in an article in Nature the discovery of tiny snippets of double-stranded RNA (dsRNA) that appeared to silence specific genes which destroyed messenger RNA, a molecule involved in the production of proteins. They hypothesised that this was caused by a catalytic process. In 2006 he shared the Nobel Prize for Medicine for helping to show the mechanism that controlled the flow of genetic information. 1959-04-27T00:00:00+0000| 27 Apr 1959 | | Andrew Z Fire was born in Stanford CA, USAFire | Carnegie Institute, Johns Hopkins, Stanford University |
Mello is a biologist who shared the 2006 Nobel Prize for Physiology or Medicine for the discovery of
RNA interference. This was based on work he carried out with colleagues to identify genes involved in regulating nematode development. He discovered that some nematode embryos injected with RNA to silence certain genes passed on the silencing effect to their offspring. On investigating further they found a double-stranded RNA was involved in the silencing phenomenon and that it is a defence mechanism against viral infection. The findings were published in 1998. 1960-10-19T00:00:00+0000| 19 Oct 1960 | | Craig C Mello was born in New Haven, CT, USAMello | University of Massachusetts |
The experiment was conducted by Sidney Brenner, Francois Jacob, and Matt Meselson and published as 'An unstable intermediate carrying information from genes to ribosomes for protein synthesis', Nature, 190 (1961), 576-81. They established the mRNA was responsible for transporting genetic information from the nucleus to the protein-making machinery in a cell. 1961-05-13T00:00:00+0000| 13 May 1961 | | Experiment confirms existence of mRNABrenner, Jacob, Meselson | University of Cambridge, Pasteur Institute, California Institute of Technology |
H Alexander and K Sprunt, 'Invasion of mammalian cells by ribonucleic acid (RNA) isolated from poliovirus', 10th International Congress of Pediatrics, Lisbon, Portugal, September 9-15, 1962.1962-09-01T00:00:00+0000| September 1962 | | Hattie Alexander and Katherine Sprunt demonstrated that the RNA of the poliovirus can independently infect human cells Alexander, Sprunt | Columbia University |
The prize was awarded to François Jacob, André Lwoff and Jacques Monod for their 'discoveries concerning genetic control of enzyme and virus synthesis'. 1965-10-14T00:00:00+0000| 14 Oct 1965 | | Nobel Prize awarded for the elucidation of the nature of mRNAJacob, Monod, Lwoff | Pasteur Institute |
Raymond Lockard and Jerry Lingrel conducted the experiment to understand the role of mRNA in the synthesis of proteins. They published their results in ‘The synthesis of mouse hemoglobin beta-chains in a rabbit reticulocyte cell-free system programmed with mouse reticulocyte 9S RNA’, Biochemical and Biophysical Research Communications, 37/2, (1969) 204-12.1969-10-08T00:00:00+0000| 8 Oct 1969 | | mRNA isolated from a rabbit introduced into mouse lymphocytes shown to stimulate production of a proteinLockard, Lingrel | University of Cincinnati |
Y Furuichi, '"Methylation-coupled" transcription by virus-associated transcriptase of cytoplasmic polyhedrosis virus containing double-stranded RNA', Nucleic Acids Research, 1, (1974), 809-22.1974-07-01T00:00:00+0000| July 1974 | | mRNA synthesis reported to be activated by a specific nucleotide during the initial stage of transcription of the double-stranded RNA genome.Furuichi | National Institute of Genetics |
Y Furuichi, K Miura (1975) 'A blocked structure at the 5' terminus of mRNA from cytoplasmic polyhedrosis virus', Nature, 253, 374-75.1975-01-31T00:00:00+0000| 31 Jan 1975 | | Unique 'cap' structure discovered at the tip end of mRNAFuruichi, Miura, Shatkin | National Institute of Genetics |
Y Furuichi, S Muthukrishnan, J Tomasz, AJ Shatkin (1976)'Caps in eukaryotic mRNAs: mechanism of formation of reovirus mRNA 5'-terminal m7GpppGm-C', Progress in Nucleic Acid Research and Molecular Biology, 19, 3-20.1976-01-01T00:00:00+0000| 1976 | | Unique 'cap' structure discovered at the tip end of mRNA Furuichi, Muthukrishnan, Tomasz, Shatkin | Roche Institute of Molecular Biology |
Monod was a French biochemist who, together with Francois Jacob, worked out the genetic control of enzyme and virus synthesis based on their experiments with Escherichia coli in the early 1960s. They proposed that a messenger molecule in cells carries codes from the DNA in the cell nucleus to the site of protein synthesis in the cell's cytoplasm. This molecule was later called messenger RNA and is now the basis of COVID-19 vaccines. Based on his work Monrod was awarded a Nobel Prize for Medicine in 1965. 1976-05-31T00:00:00+0000| 31 May 1976 | | Jacques Monod diedMonod | Pasteur Institute |
Two different scientific teams independently showed it was possible to get cells to produce rabbit globin using mRNA packaged in a liposome. The first was shown in mice cells by Giorgios J Dimtriadis at the National Institute for Medical Research. He published his achievement in 'Translation of rabbit globin mRNA introduced by Iiposomes into mouse lymphocytes', Nature, 274, 923-4. The second team, led by Marco Ostro at the University of Illinois, showed it was possible to get the protein produced in a human cell line by a team. This was published as Ostro, MJ, Giacomoni, D, Velle, et al (31 Aug 1978) ‘Evidence for translation of rabbit globin mRNA after Iiposome-mediated insertion into a human cell line’, Nature, 274, 921-23.
1978-08-31T00:00:00+0000| 31 Aug 1978 | | First proteins produced in mouse and human cells by delivering mRNA packaged in a liposome Dimitriadis, Ostro, Giacomoni, Lavelle, Paxton, Dray | National Institute for Medical Research, University of Illinois |
Stein was an American biochemist who shared the 1972 Nobel Prize for contributing to understanding the composition and functioning of ribonuclease, an enzyme that catalyses the break down of RNA into smaller components. It was the first structure and sequence worked out for any enzyme. Stein carried out the work with his colleague Stanford Moore in 1963. The two scientists were aided by their invention of the first means for automated amino acid analysis. In addition to his work on ribonuclease, Stein showed how proteins that are comprised of the same amino acids can have very different characteristics and functions.1980-02-02T00:00:00+0000| 2 Feb 1980 | | William H Stein diedStein | Rockefeller University |
Two independent teams demonstrate the phenomenon: Jonathan Izzant and Harold Weintraub; John Rubenstein and Jean-Francoise Nicolas.1984-01-01T00:00:00+0000| 1984 | | Antisense RNA shown to inhibit gene activityIzzant, Weintraub, Rubenstein, Nicolas | Fred Hutchinson Cencer Research Center, University of California San Francisco |
Synthesised by a team led by Philip Felgner at Syntex Research the lipid was a major breakthrough because natural lipids are usually negatively or neutrally charged. The new lipid formed into positively charged liposome which fused more easily with negatively charged cell membranes to deliver drugs directly into a cell. 1984-01-01T00:00:00+0000| 1984 | | First cationic (positively charged) lipid synthesised, opening up new possibilities to deliver drugs and gene therapyFelgner | Syntex Research |
PA Krieg, DA, Melton, (1984) 'Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs', Nucleic Acids Research, 12/18, 7057-70.1984-09-25T00:00:00+0000| 25 Sep 1984 | | Large amounts of biological active mRNA produced in the laboratory using RNA-synthesis vaccine Krieg, Melton | Harvard University |
Injections of a gene for pigment coloration in peturnias unexpectedly results in white flowers instead of purple flowers. US plant geneticists carrying out the experiment, Richard Jorgensen and Carolyn Napoli, call the phenomenenon 'cosuppression'.1986-01-01T00:00:00+0000| 1986 | | Discovery of RNA interference (RNAi)Jorgensen, Napoli | Advanced Genetic Sciences |
The result was published in RW Malone, PL Felgner, IM Verma (1 Aug 1989) 'Cationic liposome-mediated RNA transfection', Proceedings of the National Academy of Sciences USA, 86/16, 6077-6081.1987-01-01T00:00:00+0000| 1987 | | mRNA encapsulated into liposome made with cationic lipids injected into mouse cells shown to produce proteinsMalone, Felgner, Verna | Salk Institute for Biological Sciences, Syntex |
Started by former Hybritech executives, Vical built its business around using naked DNA for gene therapy.1987-01-01T00:00:00+0000| 1987 | | Vical Corporation foundedFelgner, | Vical |
RW Malone (Fall 1989) 'mRNA Transfection of cultured eukaryotic cells and embryos using cationic liposomes', Focus, 11/4.1987-10-01T00:00:00+0000| October 1987 | | First time mRNA encapsulated in liposome delivered into living organism demonstrated to produce proteins Malone | Salk Institute for Biological Sciences |
JA Doudna, BP Cormack, JW Szostak, 'RNA Structure, Not Sequence, Determines the 5? Splice-Site Specificity of a Group I Intron', PNAS, 86/19 (1989), 7402-06.1989-10-01T00:00:00+0000| October 1989 | | RNA demonstrated to help catalyse the process for synthesising proteinDoudna, Cormack, Szostak | Harvard University |
1990-01-01T00:00:00+0000| 1 Jan 1990 | | Experiment shows mRNA can be used to get cells to produce protein that inhibits blood clot formationKariko, Barnathan | University of Pennsylvania |
The discovery suggested the therapeutic possibility of using mRNA to transiently replace faulty or missing proteins. JA Wolff, RW Malone, P Williams, W Chong, G Acsadi, A Jani, et al.,'Direct gene transfer into mouse muscle in vivo', Science, 247 (1990) 1465–68.1990-03-23T00:00:00+0000| 23 Mar 1990 | | Naked mRNA and naked DNA injected directly into the skeletal muscle of mice reported to produce proteinsWolff, Malone, Williams, Chong, Acsadi, Jani | University of Wisconsin, Salk Institute for Biological Sciences, Vical |
GF Jirikowski, PP Sanna, D Maciejewski-Lenoir, FE Bloom, FE (1992) 'Reversal of diabetes Insipidus in Brattleboro Rats: Intrahypothalamic Injection of Vasopressin mRNA', Science, 255, 996-98.1992-02-21T00:00:00+0000| 21 Feb 1992 | | Diabetes reported to be temporarily relieved by injecting mRNA into rat brainsJirikowski, Sanna, Maciejewski-Lenoir, Bloom | Scripps Research Institute |
Holley was an American biochemist who shared the 1968 Nobel Prize for Medicine for explaining how the genetic code controls the synthesis of proteins. This stemmed from his research on RNA which he began in the late 1940s. By 1960 and he and collaborators showed that amino acids were assembled into proteins by transfer RNAs (tRNAs). In 1965 he managed to determine the composition of tRNA that incorporates the amino acid alanine into protein molecules.1993-02-11T00:00:00+0000| 11 Feb 1993 | | Robert W Holley diedHolley | Cornell University |
Lipsomes carrying mRNA encoding the influenza virus nucleoprotein reported to induce T cells in mice. F Martinon, S Krishnan, G Lenzen, R Magne, E Gomard, JG Guillet, et al.,
European Journal Immunolology, 23 (1993) 1719–22.1993-07-01T00:00:00+0000| July 1993 | | First evidence that mRNA could provide a means for vaccinesMartinon, Krishnan, Lenzen, Magne, Gomard, Guillet | INSERM |
RM Conry, AF LoBuglio, M Wright et al, 'Characterization of a messenger RNA polynucleotide vaccine vector', Cancer Research, 55 (1995), 1397-1400. 1995-04-01T00:00:00+0000| 1 Apr 1995 | | mRNA vaccine vector shown to stimulate immune response against human cancer antigenConry, LoBuglio, Wright, Sumerel, Pike, Johanning, Benjamin, Lu, Curiel | University of Alabama at Birmingham |
Anfinsen was an American biochemist who spent his career studying the relationships between structure and function in proteins. He is best known for his studies of ribonuclease, a type of nuclease that catalyses the degradation of RNA into smaller components. In 1972 he was awarded the Nobel Prize for Chemistry for his work 'on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation.'1995-05-14T00:00:00+0000| 14 May 1995 | | Christian B Anfinsen died Anfinsen | National Institutes of Health |
It was the second single RNA structure to be unravelled. Doudna, J. A. and T. R. Cech, 'Self-assembly of a Group I Intron Active Site from its Component Tertiary Structural Domains', RNA, 1/1 (1995), 36-45.1996-03-01T00:00:00+0000| March 1996 | | Jennifer Doudna and Thomas Cech unravelled structure of P4-P6 domain of the Tetrahymena thermophila group I intron ribozyme, a particular type of RNADoudna, Cech | University of Colorado |
D Boczkowski, SK Nair, D Snyder, E Gilboa, 'Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo', The Journal of Experimental Medicine, 184/2 (1996), 465-72.1996-08-01T00:00:00+0000| August 1996 | | Dendritic cells modified with mRNA shown to elicit strong immune response against tumours in miceBoczkowski, Nair, Snyder, D, Gilboa | Duke University |
The company was founded by Eli Gilboa on the back of his research at Duke University Medical School. It subsequently changed its name to Argos Therapeutics and then ColImmune. 1997-01-01T00:00:00+0000| 1997 | | Merix Bioscience founded as spin-out to develop mRNA for cancer vaccinesGilboa | Duke University |
Pirie was a virus physiologist and biochemist. He helped determine that the genetic component of viruses is RNA. Before this viruses were thought to be made up completely of proteins. During World War II he explored the possibility of extracting edible proteins from leaves, research that he carried on into the 1970s. His experiments were directed towards solving the food problem posed by the growing world population. He hoped to replace the inefficient method of feeding animals to secure protein for the diet.1997-03-29T00:00:00+0000| 29 Mar 1997 | | Norman Wingate (Bill) Pirie diedPirie | Rothamsted Experimental Station |
Introduction of RNA into cells is shown to silence genes in the nematode worm Caenorhabditis elegans. This led to the coining of the rerm 'RNA interference'. A Fire, S Xu, M K Montgomery, S A Kostas, S E Driver, C C Mello, 'Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans', Nature, 391 (1998), 806–11.1998-02-01T00:00:00+0000| February 1998 | | Double stranded RNA demonstrated to be potent mechanism for silencing genesFire, Mello, Xu, Montgomery, Kostas, Driver, | Carnegie Institution of Washington, Johns Hopkins University, University of Massachusetts Cancer Center |
Part of research to understand viral resistance in plants. A J Hamilton, D C Baulcombe, 'A species of small antisense RNA in posttranscriptional gene silencing in plants', Sciene, 29, 286/5441 (1999), 950-2.1999-01-01T00:00:00+0000| 1999 | | Discovery of small interfering RNA (siRNA), very small stretches of double-stranded RNA, interfere with genesBaulcombe, Hamilton | John Innes Centre |
I Herr, R Obst, HG Rammensee, G Jung, 'In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies', European Journal Immunology, 30/1 (2000), 1-7. 2000-01-01T00:00:00+0000| January 2000 | | Freshly synthesised naked RNA and protamine-protected RNA shown to be suitable tool for vaccinationHoerr, Obst, Ramemenseee, Jung | University of Tübingen |
The company was founded on the back of work conducted by Ingmar Hoerr.2000-01-01T00:00:00+0000| 2000 | | CureVac, a spin out company, set up to develop mRNA for vaccinesIngmar Hoerr | CureVac |
D Weissman, H Ni, D Scales, D et al, 'HIV Gag mRNA Transfection of Dendritic Cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response', The Journal of Immunology, 165 (2000), 4710-17.2000-10-15T00:00:00+0000| October 2000 | | mRNA encoding for HIV reported to activate potent T cell immune response Drew Weissman, H Ni, D Scales, Dude, Capodici, McGibney, Abdool, SN Isaacs, Cannon, Kariko | University of Pennsylvania |
Experiments conducted by Thomas Tuschl and colleagues show small interfering RNA (SiRNA) can be successfully used to induce short-term silencing of protein coding genes in mammalian cells. S M Elbashir, et al., 'Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells', Nature, 411 (2010) 494-8.2001-05-24T00:00:00+0000| May 2001 | | Small interfering RNA (siRNA) shown to be useful tool for switching off certain genesElbashir, Harborth, Lendecker, Yalcin, Weber, Tuschl | Max-Planck-Institute for Biophysical Chemistry |
The work was led by Ada Yonath using x-ray crystallography. This was a major achievement given the hundreds of thousands of atoms that ribosomes contain. Ribosomes help build proteins in the body. The work has led to many applications, including for the production of antibiotics. F Schlunzen, R Zarivach, J Harms, A Bashan, A Ticilj, R Albrecht, A Yonath, F Franceschi, 'Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria', Nature, 413 (2001), 814-21. 2001-10-25T00:00:00+0000| 25 Oct 2001 | | Structure and function of ribosomes deciphered opening up new era for improving antibiotic drugs and designing new onesYonath, Schlunzen, Zarivach, Harms, Basham, Ticilj, Albrecht, Francheschi | Weizmann Institute |
J Harms, F Schluenzen, R Zarivach et al, 'High resolution structure of the large ribosomal subunit from a mesophilic eubacterium,' Cell, 107 (2001), 679-88; PMID:11733066.2001-11-30T00:00:00+0000| 30 Nov 2001 | | Ada Yonath and colleagues published the complete high-resolution of structures of both ribosomal subunits and discovered a region important to the process of polypeptide polymerisationYonath | Weizmann Institute |
A British molecular biologist, Smith was a key pioneer in nucleic acid research. One of the few to realise the importance of nucleic acids before Watson and Crick uncovered the structure of DNA in 1953, Smith helped to elucidate the structure of ribonucleic acid molecules (RNA), the genetic material of many plant and animal viruses. This was helped by his development of paper chromatographic methods for analysing nucleosides and other units which make up DNA. He also helped to discover rare and unexpected modifications of DNA bases in bacterial genomes which are now understood to prevent attack from DNA viruses.2003-11-22T00:00:00+0000| 22 Nov 2003 | | John D Smith diedJohn D Smith | California Institute of Technology, Laboratory of Molecular Biology |
Drug developed by OPKO Opthalmologics.2004-01-01T00:00:00+0000| 2004 | | Phase I trial launched with RNAi treatment (Cand5) for wet age-related macular degeneration | |
K Karikó, H Ni, J Capodici, J, et al (2004) 'mRNA is an endogenous ligand for Toll-like receptor 3', Journal Biological Chemistry, 279, 12542–50.2004-03-01T00:00:00+0000| March 2004 | | mRNA reported to activate series of Toll-like receptors, signalling receptors of the innate immune systemKariko, Houping Ni, Capodici, Lamphier, Drew Weissman | University of Pennsylvania |
K Karikó, M Buckstein, H Ni, D Weissman, D (Aug 2005) 'Suppression of RNA recognition by toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA', Immunity, 23/2, 165-75.2005-08-01T00:00:00+0000| August 2005 | | mRNA rendered invisible to immune system by replacing its nucleoside uridine with pseudouridineKariko, Buckstein, Houping Ni, Drew Weissman | University of Pennsylvania |
The system was devised by Ian MacLachlan in collaboration with Pieter Cullis. They first published the technique as 'Diffusible-PEG-Lipid Stabilized Plasmid Lipid Particles', Advanced Genetics (2005), 53PA:157-188. doi: 10.1016/S0065-2660(05)53006-2.2005-10-19T00:00:00+0000| 19 Oct 2005 | | Lipid nanoparticle system published for delivering drugs and gene therapyMacLachlan, Cullis | Protiva Biotherapeutics, Inex Pharmaceuticals |
Awarded to Andrew Fire and Craig C Mello for their work on RNAi in the nematode worm Caenorhabditis elegans published in 1998.2006-01-01T00:00:00+0000| 2006 | | Nobel Prize awarded for RNA inteference workFire, Mello | Carnegie Institution of Washington, University of Massachusetts |
The company was founded by Drew Weissmann and Katalin Karikó.2006-01-01T00:00:00+0000| 2006 | | Spin-out company, RNARx, founded to commercialise modified mRNA for anaemia treatmentKariko, Drew Weissman | |
TS Zimmerman, ACH Lee, A Akinc, et al (26 March 2006) 'RNAi-mediated gene silencing in non-human primates', Nature, 441, 111-14.2006-03-26T00:00:00+0000| 26 Mar 2006 | | Monkey studies show lipid nanoparticle system successfully delivered RNA to silence disease causing genesZimmerman, ACH Lee, Akinc, Bramlage, Bumcrot, Fedorik, Harborth, James Heyes, Lloyd Jeffs, Matthias John, Adam Judge, Kieu Lam, Kevin McClintock, Nechev, Lorne Palmer, Racie, Ingo Rohl, Seiffert, Shannmugam, Sood, Soutschek, Toudjarska, Wheat, Yaworski, Z | Protiva Biotherapeutics |
Merck gains access to potentially gate-keeping RNAi patents owned by Sima. Signals high hopes for RNAi technology.2006-10-01T00:00:00+0000| October 2006 | | Merck acquires Sima Therapeutics for US$1.1 billion | |
S Holtkamp, S, Kreiter, A Seimi, A, et al (15 Dec 2006) 'Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells', Blood, 108/13, 4009-17.2006-12-15T00:00:00+0000| 15 Dec 2006 | | Method published to produce mRNA with increased stability and translational efficiencyHoltkamp, Sebastian Kreiter, Abderraouf Selmi, Petra Simon, Koslowski, Christoph Huber, Tureci, Sahin | Johannes-Gutenberg University |
Roche pays US$331 million for limited access to RNAi therapeutic platform.2007-01-01T00:00:00+0000| 2007 | | Roche signs alliance with Alynlam for RNAi therapeutics | |
Kornberg was an American biochemist renowned for his research on enzymes which create DNA. In 1956 he and his team isolated the first enzyme known to be involved in the replication of DNA. It would be called DNA polymerase I. For this work Kornberg shared the 1959 Nobel Prize for Medicine. The Prize was given for the discovery of the 'mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.'2007-10-26T00:00:00+0000| 26 Oct 2007 | | Arthur Kornberg diedKornberg | Stanford University |
The company, originally called TRON, was founded by Ozlem Tureci, Ugur Sahin and Christoph Huber.2008-01-01T00:00:00+0000| 2008 | | Biopharmaceutical New Technologies (BioNTech) founded to develop mRNA as personalised cancer immunotherapiesSahin, Tureci, Huber | BioNTech |
Drug poor at preventing vision loss.2009-01-01T00:00:00+0000| 2009 | | Phase III clinical trials for RNAi treatment (Cand5) for wet age-related macular degeneration halted | |
Zamecnik was an American scientist who pioneered the in vitro synthesis of proteins and helped determine the way cells generate proteins. Together with Mahlon Hoagland and Mary Stephenson he showed that protein synthesis was activated by adenosine 5'-triphosphate and that ribosomes were the site of protein assembly. He also subsequently helped to discover transfer RNA and is credited with laying the foundation for the development of antisense therapies, a type of gene therapy.
2009-12-27T00:00:00+0000| 27 Dec 2009 | | Paul Zamecnik diedZamecnik | Massachusetts General Hospital |
Sends shockwaves through RNAi drug development community.2010-11-01T00:00:00+0000| November 2010 | | Disappointment follows Roche's decision to pull out of RNAi therapeutics | |
2010-11-01T00:00:00+0000| November 2010 | | Moderna Therapeutics founded to commercialise modified mRNA vaccines and therapeuticsRossi, Kernneth Chien, Robert Langer | Moderna |
L Warren, PD Manos, T Ahfeldt, T et al (5 Nov 2010) 'Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA', Cell Stem Cell, 7/5, 618-30.2010-11-05T00:00:00+0000| 5 Nov 2010 | | Modified mRNA reported to transform skin cells into pluripotent stem cellsLuigi Warren, Philip Manos, Ahfeldt, Ahfeldt, Yuin-Han Loh, Hu Li, Frank Lau, Wataru Ebina, Pankaj Mandal, Zachary Smith, Meissner, George Daley, Brack, James Collins, Chad Cowan, Schlaeger, Rossi | Harvard University |
Merck gained facility from Sima Therapeutics. Decision driven by company's need to cut costs.2011-07-29T00:00:00+0000| July 2011 | | Merck closes down RNAi research facility | |
Study conducted with 41 patients with advanced cancer. Led by Josep Tabernero, Institute of Oncology Department, Vall d'Hebron University together with Alnylam and other cancer research centres.2013-02-11T00:00:00+0000| 11 Feb 2013 | | RNAi treatment shown to be effective cancer treatment in phase I clinical trialsTabernero | Vall d'Hebron University |
The team who did the research was led by Kenneth Chien. L Zangi, KO Lui, A von Gise, et al, 'Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction', Nature Biotechnology, 31/10 (Oct 2013), 898-907.2013-10-01T00:00:00+0000| October 2013 | | Modified mRNA shown to help improve heart function in miceLior Zangi, Kathy Lui, von Gise, Qing Ma, Ebina,Ptaszek, Spater, Huansheng Xu, Tabebordbar,Gorbatov, Sena, Nahrendorf, David Briscoe,Ronald Li, Amy Wagers, Rossi, William Pu, Kenneth Chien | Harvard University, Massachusetts General Hospital, Children's Hospital Boston, Mount Sinai School of Medicine, Karolinska Institute |
The drug, developed by Alynylam, aimed at lowering cholesterol. It was tested in 32 patients. 2013-10-03T00:00:00+0000| 3 Oct 2013 | | RNAi drug was indicated to be safe and well-tolerated in a phase I trial | |
Sanofi pays US$700 million for 12 percent stake in Alynlam. Signals renewed interest in RNAi therapeutics.2014-01-01T00:00:00+0000| January 2014 | | Sanofi invests in Alynlam | |
Roche agreed to pay US$148 million in upfront and milestone payments. Deal signals renewed optimism in RNAi therapeutics.2014-01-10T00:00:00+0000| January 2014 | | Roche entered RNAi therapeutics alliance with Santaris | |
Novartis shut down its collaborative programme with Alynlam based on lingering problems associated with delivering RNAi therapeutics. It marked a major set back for the RNAi therapeutics field as a whole. 2014-04-14T00:00:00+0000| 14 Apr 2014 | | Novartis suddenly pulls plug on RNAi research | Novartis |
The trials undertaken from 2013 used a drug that interferes with RNA. The drug was developed by Arrowhead Pharmaceuticals. The aim of the drug is to reduce the surface antigens (HBsAg) created by chronic hepatitis B infections. The trials showed the experimental drug was safe and effective enough to be tested in people. The drug is designed to deliver a molecule to the liver where it binds to a receptor, and then another molecule, derived from bee venom, helps break through the membranes in the liver cells to deliver the medicine directly into the cells. The drug interferes with the the expression of the hepatitis B messager RNA that produces HBsAg. 2015-01-01T00:00:00+0000| 2015 | | Chimpanzee trials indicated that gene silencing drug could treat hepatitis B | Arrowhead Pharmaceuticals |
Launched by Isis Pharmaceuticals (now Ionis) in partnership with Roche, the trial aimed to study the first therapy designed to silence the Huntingdon's disease gene and reduce the production of a protein responsible for the disease. 2015-07-21T00:00:00+0000| 21 Jul 2015 | | Phase 1 clinical trial launched with RNAi treatment for Huntingdon's disease | Isis Pharmaceuticals, Roche |
2016-11-09T00:00:00+0000| 9 Nov 2016 | | FDA halted phase II trials with RNA interference drug, ARC-520, due to multiple deaths of non-human primates treated with high doses | Arrowhead Pharmaceuticals |
The company's shares fell from a high of $6.18 on November 8, 2016, to an $1.20 on December 21, 2016. 2016-11-09T00:00:00+0000| 9 Nov 2016 - 21 Dec 2016 | | Arrowhead Pharmaceuticals shares fell following hold on clinical trials with RNAi drug to treat hepatitis B | Arrowhead Pharmaceuticals |
227 patient study showed drug from Alnylam Pharmaceuticals had benefits for rare hereditary disorder - ATTR amyloidosis with polyneuropathy, a rare disorder.2017-09-20T00:00:00+0000| 20 Sep 2017 | | Positive results reported from clinical trial with RNAi drug | Alynlam |
The method provided a means to fix genetic mutations without tampering with the genome. It was published in D.B.T. Cox, J.S. Gootenberg, O.O. Abudayyeh, B.Franklin, M.J. Kellner, et al, 'RNA editing with CRISPR-Cas13', Science (25 Oct 2017), eaaq0180, DOI: 10.1126/science.aaq01802017-10-25T00:00:00+0000| 25 Oct 2017 | | New CRISPR technique published for editing RNA Zhang, Cox, Gootenberg, Abudayyeh, B Franklin, Kellner, Essletzbichler, Verdine, Joung, Lander, Belanto, Voytas, Regev | Massachusetts Institute of Technology, University of Minnesota |
N Pardi, MJ Hogan, FW Porter, D Weismann, 'mRNA vaccines — a new era in vaccinology', Nature Reviews: Drug Discovery, 17 (2018), 261-79.2018-01-12T00:00:00+0000| 12 Jan 2018 | | mRNA flagged up as promising new vaccine technology for combating infectious diseasesPardi, Michael Hogan, Frederick Porter, Drew Weismann | University of Pennsylvania |
The aim of the drug is to mute hepatitis B genes to give the immune system a chance to fight the hepatitis B infection.2018-03-27T00:00:00+0000| 27 Mar 2018 | | Dosing trial launched with humans to test use of RNA interference drug to treat hepatitis B | Arrowhead Pharmaceuticals |
Developed by Arrowhead Pharmaceuticals, the drug, ARC-520, is administered with the antiviral entecavir. The treatment cleared the HBsAg from one patient and substantially reduced it in the remaining patients. The results were presented to the European Association for the Study of the Liver. 2018-05-02T00:00:00+0000| 2 May 2018 | | Positive results for RNAi drug for treating chronic hepatitis b reported from 8-person clinical trial | Arrowhead Pharmaceuticals |
The drug, patisiran, was approved for the treatment of a rare, progressive polyneuropathy caused by hereditary transthyretin-mediated, which affects approximately 50,000 people worldwide. Developed by Alynylam Pharmaceuticals, patisiran targets mRNAs for mutated transthyretin, which causes peripheral amyloidosis. The drugs works by delivering small interfering RNAs to the liver where they bind and degrade transthyretin messenger RNA. 2018-08-14T00:00:00+0000| 14 Aug 2018 | | FDA approved first-ever drug based on RNAi | Alynylam Pharmaceuticals |
A chemist and biophysicist, Klug won the 1982 Nobel Prize in Chemistry for the development of crystallographic electron microscopy. He used the technique to investigate nucleic acid-protein complexes and the structure of viruses. He developed an interest in viruses after meeting Rosalind Franklin in late 1953. Klug also discovered zinc-finger proteins, a class of proteins that bind specific DNA sequences. Scientists now use the modular nature of these proteins to design synthetic proteins for targeted therapies. Klug left Lithuania for South Africa with his Jewish parents when he was two. He went to England after completing his master's degree. Klug was the director of the Laboratory of Molecular Biology (1986-1996) and President of the Royal Society (1995-2000).2018-11-20T00:00:00+0000| 20 Nov 2018 | | Aaron Klug diedKlug | Birkbeck College, Laboratory of Molecular Biology |
The vaccine was developed by BioNTech in partnership with Pfizer.2020-12-11T00:00:00+0000| 11 Dec 2020 | | FDA approved first mRNA vaccine for COVID-19 for emergency use | BioNTech, Pfizer |
The vaccine was developed by Moderna. 2020-12-18T00:00:00+0000| 18 Dec 2020 | | FDA approved second mRNA vaccine for COVID-19 | Moderna |
Altman was a Canadian molecular biologist who shared the 1989 Nobel Prize for Chemistry for discovering the catalytic properties of RNA. This emerged out of some work Altman carried out between 1978 and 1983 on a bacterial enzyme called RNAs-P. His research helped transform the basic understanding of nuclear acids, which up to this moment had been understood to only carry genetic information. It also opened up the possibility of using genetic engineering to develop new forms of therapy against viral infections. 2022-04-05T00:00:00+0000| 5 Apr 2022 | | Sidney Altman diedAltman | Harvard University, Laboratory of Molecular Biology, Yale University |
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