A plasmid is a small double-stranded unit of DNA, usually circular but sometimes linear, that exists independent of the chromosome and is capable of self-replication. Each plasmid carries only a few genes.
This shows an electon microscope image of DNA of the pSC101 plasmid, which was used as a vector in the first successful DNA cloning experiments, published in SN Cohen, ACY Chang, HW Boyer, RB Helling. 'Construction of biologically functional bacterial plasmids in vitro', PNAS USA, 70/11 (1973), 3240–4. Credit: Stanley N Cohen.
Connections Stanley Cohen
Plasmids come in many different sizes and are used for many different purposes in biotechnology. They first made their mark in the field of recombinant DNA in the 1970s, being used as a tool to insert genes into bacteria to encourage their production of therapeutic proteins such as human insulin.
In more recent years plasmid DNA has begun to be investigated as a therapeutic platform for treating infectious, genetic and acquired diseases. Plasmid DNA is seen, for example, as a promising tool for the development of DNA vaccines against HIV-AIDS, Ebola, Malaria, enteric pathogens, and influenza. The plasmid is genetically modified to produce one or two specific proteins from a pathogen and then purified for immunisation. DNA vaccines offer several advantages over traditional vaccines. Firstly, they eliminate the need to inject infectious agents. Secondly, they stimulate both B- and T-cell immune responses. Thirdly, they are more stable in different temperatures so are easier to store and transport. Lastly, they can be manufactured on a large-scale and at low cost.
The development of plasmids as vaccines poses significant challenges. Most DNA vaccines tested in experimental trials have so far evoked too weak an immune response in humans to protect against disease. Positive results, however, were announced in 2006 from preliminary clinical trials conducted with a DNA vaccine developed against H5N1 avian flu. Plasmids are also being explored for the development of DNA vaccines for non-treatable neurological disorders, such as ischemic stroke, Parkinson's disease, Alzheimer's disease and multiple sclerosis. A preliminary study of DNA vaccination against multiple sclerosis, completed in 2007, indicates the approach could be effective for this disease. More extensive trials, however, are needed to confirm the viability of DNA plasmids and their use for DNA vaccines.
Independent strands of DNA were first found in bacterial cells in the late 1940s by researchers investigating how bacteria become resistant to antibiotics and how traits are passed on to offspring by phages (viruses of bacteria) and DNA structures other than chromosomes. Various names were applied to these DNA strands during this time, including pangenes, bioblasts, plasmagenes, plastogenes, choncriogenes, cytogenes, proviruses, and episomes.
The word 'plasmid' was first coined by Joshua Lederberg in 1952. He used it to describe 'any extrachromosomal hereditary element'. Lederberg first used the term in a paper he published describing some experiments he and his graduate student Norton Zinder conducted on Salmonella bacteria and its virus P22. During the course of this work they observed that virus particles could somehow pick up bacterial genes and transfer them to another host, a process they called transduction. Yet, how this phenomenon worked and what lay behind remained poorly understood for many years. This changed following the unveiling of the double-helix structure of DNA in 1953, which proved that DNA was made up of genetic material. Soon after scientists began to determine that plasmids were made up of small sequences of DNA which helped them to pass on particular traits.
By the 1960s a number of plasmids had been identified. This included fertility plasmids first observed in the late 1940s by Esther Lederberg, Joshua's wife, which carry the fertility genes necessary for bacterial conjugation. Another group were resistance (R) plasmids which carry the genes that encode resistance to antibiotics or poisons. It was an R plasmid (pSC101) that proved instrumental to the generation of the first recombinant DNA molecule.
A plasmid is a strand or loop of DNA that is typically found in bacteria as well as archae (single-cell organisms) and eukarya (organisms of complex cell structure). Plasmids carry only a few genes and exist independently of chromosomes, the primary structures that contain DNA in cells. Able to self-replicate, plasmids can be picked up from the environment and transferred between bacteria.
Plasmids are used by their host organism to cope with stress-related conditions. Many plasmids, for example, carry genes that code for the production of enzymes to inactivate antibiotics or poisons. Others contain genes that help a host organism digest unusual substances or kill other types of bacteria.
Several characteristics of plasmids make them easy to modify genetically. Firstly, they have relatively small DNA sequences, between 1,000 and 20,000 DNA base pairs. Secondly, they are easy to cut open, without falling apart, and snap back into shape. This makes it easy to insert new DNA into plasmids. Once a new DNA is inserted, the modified plasmid can be grown in bacteria for self-replication to make endless copies.
The ease of manipulation and reproduction of plasmids, as well as their long-term stability, has made them indispensable tools in genetics and biotechnology laboratories. One of their most important functions is as a delivery vehicle, or vector, to introduce foreign DNA into bacteria, a fundamental step for genetic engineering and many other biotechnology applications.
Plasmid: timeline of key events
|17 Sep 1922||Naomi Datta was born in London, UK||Datta||Hammersmith Hospital|
|23 May 1925||Joshua Lederberg was born in Montclair, NJ, USA||Joshua Lederberg||University of Wisconsin|
|24 Jan 1934||Stanley Falkow was born in Albany, New York, USA||Falkow||Georgetown University School of Medicine, University of Washington School of Medicine, Stanford University|
|1963 - 1965||Increasing use of antibiotics noted to contribute to rapid rise of antimicrobial resistance in enterobacteria||Naomi Data, ES Anderson||Enteric Reference Laboratory|
|March 1963||Concerns about antimicrobial resistance mount after discovery that bacteria can pick up resistance genes from small self-replicating DNA in the environment known as plasmids.||Watanabe||Keito University|
|27 Nov 1965||Plasmids noted to carry genes conveying antibiotic resistance in bacteria||Anderson, Datta|
|2 Feb 2008||Joshua Lederberg died||Joshua Lederberg||University of Wisconsin|
|30 Nov 2008||Naomi Datta died||Datta||Hammersmith Hospital|
|5 May 2018||Stanley Falkow died||Falkow||Georgetown University School of Medicine, University of Washington School of Medicine, Stanford University|
17 Sep 1922
Naomi Datta was born in London, UK
23 May 1925
Joshua Lederberg was born in Montclair, NJ, USA
24 Jan 1934
Stanley Falkow was born in Albany, New York, USA
1963 - 1965
Increasing use of antibiotics noted to contribute to rapid rise of antimicrobial resistance in enterobacteria
Concerns about antimicrobial resistance mount after discovery that bacteria can pick up resistance genes from small self-replicating DNA in the environment known as plasmids.
27 Nov 1965
Plasmids noted to carry genes conveying antibiotic resistance in bacteria
2 Feb 2008
Joshua Lederberg died
30 Nov 2008
Naomi Datta died
5 May 2018
Stanley Falkow died