Sunday, January 11, 2015

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)

CRISPR (Clustered Regularly Inter-spaced Short Palindromic Repeats), is a basic acronym for DNA loci that contain multiple, short, direct repetitions of base sequences. Each repetition contains a series of base pairs followed by the same or a similar series in reverse and then by thirty or so base pairs known as 'spacer DNA.' The spacers are short segments of DNA from a virus and serve as a 'memory' of past exposures. CRISPRs are found in the genomes of approximately 40% of sequenced eubacteria and 90% of sequenced archaea. CRISPR's are often associated with cas genes which code for proteins that perform various functions related to CRISPRs. The CRISPR-Cas system functions as a prokaryotic immune system, in that it confers resistance to exogenous genetic elements such as plasmids and phages and provides a form of acquired immunity. CRISPR spacers recognize and silence exogenous genetic elements in a manner analogous to RNAi in eukaryotic organisms. Since 2012, the CRISPR-Cas system has been used for a novel technique of gene editing (silencing, enhancing or changing specific genes) which even works in eukaryotes. By inserting a plasmid containing cas genes and specifically designed CRISPRs, the organisms genome can be cut at any desired location. (2) See: http://en.wikipedia.org/wiki/CRISPR
Microinjection of embryos with TALEN mRNA 
The Biochemical Society noted the following in an announcement of a focused meeting entitled: CRISPR: Evolution, Mechanisms and Infection:

"The extreme evolutionary pressure exerted on cells by viruses, and vice verse, is a key driving force in evolution. Perhaps the most exciting development in this area in the past ten years is the discovery of the CRISPR system for antiviral defence. These clusters of regularly inter-spaced palindromic repeats are genomically encoded by many prokaryotes and carry a record of past viral infections. Transcription and processing of the CRISPR RNA leads to RNA-directed cleavages of the nucleic acid of invading mobile elements, mediated by large, complex molecular machines assembled from CRISPR associated (Cas) proteins. The process of viral DNA capture and incorporation int CRISPR loci is still enigmatic and is an interesting example of pure Lamarckian evolution. The dynamic interplay between viruses and hosts also has clear parallels to the predator: prey relationship studied more widely in biology. CRISPRs are the most rapidly evolving parts of most prokaryotic genomes, providing opportunities for the study of evolution in the field in real time." See: http://www.biochemistry.org/tabid/379/MeetingNo/SA148/view/Conference/default.aspx

The applications of CRISPR will likely revolutionize genetic engineering, allowing scientists to engineer any part of the human genome with exceptionally accurate precision. Caribou Biosciences, a Berkeley based company, specializes in utilizing the Cas9 enzym, an extremely efficient genome editing platform. Dr. Haurwitz, of Caribou noted: "I would say that Cas9, like other site-specific genome engineering technologies such as TALENs (transcription activator-like effector nucleases) or ZFNs (zinc finer nucleases), does have the capability of being deployed appropriately in a therapeutic context to modify patients cells at the genomic level in order to either repair disease causing genes or otherwise prevent infections. For example Sangamo Biosciences, which is a company here in the Bay Area, has clinical trials ongoing where they are using ZFN technology to modify T-cells or stem cells in order to knock out the receptor that is necessary for HIV infections. So they are using site specific genome engineering technology with the ultimate goal of curing HIV. In terms of Cas9 specific therapeutic applications, I think there is tremendous opportunity. I also think the trickiest part is not actually editing the cells. There are a number of technologies for editing the cells; it's appropriately and safely delivering the editing technology that is the tricky part." See: http://getsynbio.com/dr-rachel-haurwitz-caribou-biosciences/

It will be interesting to follow Caribou Biosciences as a forerunner in Cas9 and I will update this as things progress.


Dr.Jill Bellamy is an internationally recognized expert on biological warfare and defence. She has formerly advised NATO and for the past seventeen years has represented a number of bio-pharmaceutical and government clients working on procurement strategy between NATO MS and Washington DC. Her private government relations consultancy Warfare Technology Analytics is based in the Netherlands. Dr. Bellamy's articles have appeared in the National Review, The Wall Street Journal, The Washington Post, The Sunday Times of London, Le Temps, Le Monde and the Jerusalem Post among other publications. She is a CBRN SME with the U.S. Department of Defence, Chemical, Biological, Radiological and Nuclear Defence Information Analysis Center and CEO of Warfare Technology Analytics.

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