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.
