RNA -
guided gene drives based on CRISPR / Cas9 have generated considerable excitement as a potential means of addressing otherwise intractable ecological problems.
The primary limitation of RNA -
guided gene drives is that they are likely to spread to fixation in all populations connected by gene flow.
RNA -
guided gene drives can theoretically be used to delete any existing gene, to edit any gene important for fitness, or to add new transgenes.
The recent development of the CRISPR / Cas9 system for genome editing enables the construction of RNA -
guided gene drives that may be capable of spreading nearly any alteration that can be made with Cas9.
RNA -
guided gene drives could also cause a population crash due to the buildup of recessive mutations causing infertility or inviability or by biasing the sex ratio.
Cas9 may enable «RNA -
guided gene drives» to edit nearly any gene in sexually reproducing populations (1).
RNA -
guided gene drives can efficiently and reversibly bias inheritance in wild yeast.
RNA -
guided gene drive elements could address many ecological problems by altering the traits of wild organisms, but the likelihood of global spread tremendously complicates ethical development and use.
Not exact matches
One route, first suggested by Burt in 2003, is to release a sequence that is resistant — effectively unrecognizable — to the
guiding enzyme that finds cuts of DNA in a
gene drive.
When an egg or sperm carrying hte
gene drive fuses with another egg or sperm, the enzyme and
guide RNA are made to cut the
gene and start the process over.
These new
drives insert
genes that produce the components of the system: a cutting enzyme and an RNA to
guide it to the proper cutting site.
When creating the antimalaria antibody
gene drive, the researchers had to inject Cas9,
guide RNAs and bits of DNA containing the
gene drive into the egg.
The finding may also
guide future discoveries of meiotic
drive genes in other organisms, such as crops or humans.
They ultimately zeroed in on three specific NOD2 -
driven inflammation
genes (SLC26a, MARCKSL1, and RASGRP1) that
guided investigators in finding the most effective compounds.
The committee recommended a phased testing approach to
gene drive research to
guide research from the laboratory to the field.
The team has outlined in the eLife publication numerous precautionary measures intended to
guide the safe and responsible development of
gene drives, many of which were not possible with earlier technologies.
Genomic changes can be reversed with subsequent
gene drives, though the cassette encoding the
guide RNAs and possibly cas9 will remain and any ecological changes resulting from the original genomic alteration will not necessarily be reversed.
This could be remedied by using a threshold - dependent underdominance
gene drive to «recode» specific sequences of a local population, which then could be selectively targeted for removal using a subsequent RNA -
guided suppression
drive.
Importantly, our divergent
guide RNAs will also enable global CRISPR
gene drive elements to overcome the problem of instability caused by including multiple repetitive
guide RNA sequences in the
drive cassette [34], which in turn is required in order to overcome
drive - resistant alleles [35].