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. Their development 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 in these years, including pangenes, bioblasts, plasmagenes, plastogenes, choncriogenes, cytogenes, proviruses, and episomes. The word 'plasmid' was first coined by Joshua Lederberg in 1952, who used it to describe 'any extrachromosomal hereditary element'. His use of the word appeared in a paper 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. How this phenomenon worked and what lay behind it was poorly understood before the unravelling of the structure or function DNA in 1953 which confirmed DNA to be the only 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.
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.
This section was put together by Lara Marks with Dmitriy Myelnikov based on his PhD thesis 'Transforming mice: technique and communication in the making of transgenic animals, 1974-1988', Cambridge University, 2015.
Plasmid: timeline of key events
23 May 1925
Joshua Lederberg was born in Montclair, NJ, USA
2 Feb 2008
Joshua Lederberg died