By Bio-IT World Staff
July 18, 2014 | In a paper published yesterday in the open access journal eLife, George Church and colleagues discuss the potential for "gene drives" that alter the genomes of whole wild populations using CRISPR gene editing technology, and weigh the risks and public interests surrounding such initiatives. Church's lab at the Wyss Institute for Biologically Inspired Engineering at Harvard Medical School has been involved in the development of CRISPR since it first took off as a gene editing tool two years ago.
Gene drives have been imagined and even attempted for over a decade, traditionally with disease-carrying species of mosquito as their targets. A gene drive takes advantage of mechanisms of biased inheritance, in which a genetic element is favored to be passed on to the next generation even if it confers no adaptive advantage, or even harms the host organism. Such genetic elements could include endonucleases, which seek out a target region of a chromosome, cut out the native sequence, and copy themselves in its place; or segregation distorters, which destroy entire homologous chromosomes during cell division, leaving only their own copies intact. Although no gene drive has yet advanced beyond the lab, a transgenic swarm of mosquitoes without a gene drive was released in Brazil earlier this year as a control measure against dengue fever.
In the eLife paper, "Concerning RNA-guided gene drives for the alteration of wild populations," Church and his colleagues note that CRISPR will make it much easier for a far wider variety of labs to engineer future gene drives in any species they choose. CRISPR is more specific, more durable after multiple replications, and easier to target to a chosen site on the genome than any previous gene editing technique. Writing that "we hope to initiate transparent, inclusive, and well-informed discussions concerning the responsible evaluation and application of these nascent technologies," the authors consider in detail how multiple obstacles to a CRISPR-based gene drive could be addressed. They also float a number of real-world applications, including the control of disease vectors, elimination of invasive species, and agricultural pest control.
The authors further note that a successful gene drive, once released into the wild, would be difficult to control and would not respect any artificial boundaries like political borders in spreading through a species. They make certain broad suggestions for responsible conduct of gene drives, including education and engagement of the public. "[A]ll decisions involving the use of suppression drives must involve extensive deliberations including but not limited to ecologists and citizens of potentially affected communities," they write.
More specifically, the authors list certain precautions that any lab considering a gene drive could take to make the effects as precise and reversible as possible. They propose field trials with small populations that contain any desired genetic changes, but not the gene drives to favorably spread them, in order to observe the ecological impacts of the modified organisms. They also insist that after a gene drive is released, wild samples should be captured and sequenced periodically to monitor how the relevant genes are dispersing through the population, and "recommend that all laboratories seeking to build standard gene drives capable of spreading through wild populations simultaneously create reversal drives able to restore the original phenotype."
"These precautions," they add, "would allow the effects of an accidental release to be swiftly if partially counteracted."
A more complete discussion of how CRISPR was discovered, and how it changes the picture for gene editing, can be read in "Gene Therapy's Next Generation."