Friday, June 5, 2015


As described in a recent article in Nature, the advent of a powerful gene editing technique based on the CRISPR-Cas9 system is leading to a revolution in molecular biology and possibly in medicine. For a couple of decades scientists have known how to introduce or modify genes in cells by a process called homologous recombination.  When done in stem cells, the gene modified cells can be re-implanted and can give rise to tissues, including reproductive tissues, and thus eventually to genetically modified organisms. A major problem is that the entire process is very inefficient. Several previous attempts to increase the efficiency of gene editing have involved ‘designed’ proteins such as the Talens nucleases or zinc finger nucleases that can cut DNA at specific sites thus creating opportunities for recombination. However, preparing these designed proteins is difficult and time consuming.

The great advantage of the CRISPR-Cas system is that it uses a short RNA molecule to target the site in DNA that needs to be cut, with the cutting provided by the Cas enzyme.  It’s easy to design RNAs that can hybridize with specific DNA sites, and the entire CRISPR-Cas system can be engineered into a viral vector that is also quite easy to use.  Thus this approach has revolutionized laboratory practices for gene modification in cells for basic research purposes.

CRISPR can also impact in vivo studies. For example, an animal with a gene defect can provide stem cells. The stem cell gene can be ‘corrected’ in the lab using CRISPR and the corrected stem cells re-infused into animals. Potentially the stem cells can then engraft in tissues and thus fully or partially correct the defect in the animal. This has already been done in a number of studies in mice.  Obviously the same is potentially possible in humans but has not yet been done.  Some investigators have tried to correct genetic defects in mice by directly injecting the entire CRISPR-Cas9 system, but this is very inefficient in its current state of development.

The very power of this technique is beginning to cause ethical concerns. For example a group in China reported editing the genes of human embryos. The potential for this type of activity has caused leading scientists in CRISPR research to advocate restraint and careful design of projects to avoid risks to humans.

The CRISPR-Cas technology clearly has enormous potential. However, it needs to be viewed in the same perspective as all new biomedical technologies. Monoclonal antibodies, siRNA, nanomedicine- each of these potentially transformative technologies has followed the same path, with an initial period of almost irrational exuberance, followed by disillusionment as problems inevitably emerged, followed by a more considered assessment of ultimate therapeutic potential. So will it be with CRISPR.  

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