It’s very peculiar being able to understand each word individually in clustered regularly interspaced short palindromic repeats (CRISPR) but not being able to puzzle out much meaning other than the widely known ‘it’s a gene editor’.
Regardless, CRISPR is a powerful gene editing tool and that can lead to trouble. Even before CRISPR, we’ve had some genetic accidents. Perhaps the best known is the ‘killer bee’ or Africanized bee (from its Wikepedia entry),
The Africanized bee, also known as the Africanised honey bee, and known colloquially as “killer bee”, is a hybrid of the western honey bee species (Apis mellifera), produced originally by cross-breeding [emphasis mine] of the East African lowland honey bee (A. m. scutellata) with various European honey bees such as the Italian honey bee A. m. ligustica and the Iberian honey bee A. m. iberiensis.
The Africanized honey bee was first introduced to Brazil in 1956 in an effort to increase honey production, but 26 swarms escaped quarantine in 1957 [emphasis mine]. Since then, the hybrid has spread throughout South America and arrived in North America in 1985. Hives were found in South Texas of the United States in 1990.
Africanized bees are typically much more defensive than other varieties of honey bee, and react to disturbances faster than European honey bees. They can chase a person a quarter of a mile (400 m); they have killed some 1,000 humans, with victims receiving ten times more stings than from European honey bees. They have also killed horses and other animals.
Getting back to how powerful CRISPR is, a group of scientists has developed a set of strategies for safeguarding gene drive experiments (from a January 22, 2019 eLife press release also on EurekAlert),
Researchers have demonstrated for the first time how two molecular strategies can safeguard CRISPR gene drive experiments in the lab, according to a study published today in eLife.
Their findings, first reported on bioRxiv, suggest that scientists can effectively use synthetic target sites and split drives to conduct gene drive research, without the worry of causing an accidental spread throughout a natural population.
Gene drives, such as those trialled in malaria mosquitoes, are genetic packages designed to spread among populations. They do this via a process called ‘drive conversion’, where the Cas9 enzyme and a molecule called guide RNA (gRNA) cut at a certain site in the genome. The drive is then copied in when the DNA break is repaired.
“CRISPR-based gene drives have sparked both enthusiasm and deep concerns due to their potential for genetically altering entire species,” explains first author Jackson Champer, Postdoctoral Fellow in the Department of Biological Statistics and Computational Biology at Cornell University, New York. “This raises the question about our ability to prevent the unintended spread of such drives from the laboratory into the natural world.
“Current strategies for avoiding accidental spread involve physically confining drive-containing organisms. However, it is uncertain whether this sufficiently reduces the likelihood of any accidental escape into the wild, given the possibility of human error.”
Two molecular safeguarding strategies have recently been proposed that go beyond simply confining research organisms. The first is synthetic target site drive, which homes into engineered genomic sites that are absent in wild organisms. The second is split drive, where the drive construct lacks a type of enzyme called the endonuclease and relies instead on one engineered into a distant site.
“The nature of these strategies means that they should prevent an efficient spread outside of their respective laboratory lines,” Champer adds. “We wanted to see if they both had a similar performance to standard homing drives, and if they would therefore be suitable substitutes in early gene-drive research.”
To do this, the team designed and tested three synthetic target site drives in the fruit fly Drosophila melanogaster. Each drive targeted an enhanced green fluorescent protein (EGFP) gene introduced at one of three different sites in the genome. For split drives, they designed a drive construct that targeted the X-linked gene yellow and lacked Cas9.
Their analyses revealed that CRISPR gene drives with synthetic target sites such as EGFP show similar behaviour to standard drives, and can therefore be used for most testing in place of these drives. The split drives demonstrated similar performance, and also allow for natural sequences to be targeted in situations where the use of synthetic targets is difficult. These include population-suppression drives that require the targeting of naturally occurring genes
“Based on our findings, we suggest these safeguarding strategies should be adopted consistently in the development and testing of future gene drives,” says senior author Philipp Messer, Assistant Professor in the Department of Biological Statistics and Computational Biology at Cornell University. “This will be important for large-scale cage experiments aimed at improving our understanding of the expected population dynamics of candidate drives. Ultimately, this understanding will be crucial for discussing the feasibility and risks of releasing successful drives into the wild, for example to reduce malaria and other vector-borne diseases.”
Here’s a link to and a citation for the paper,
Molecular safeguarding of CRISPR gene drive experiments by Jackson Champer, Joan Chung, Yoo Lim Lee, Chen Liu, Emily Yang, Zhaoxin Wen, Andrew G Clark, Philipp W Messer. DOI: 10.7554/eLife.41439 Short Report Jan 22, 2019
This paper is open access. For anyone who doesn’t mind reading an earlier version of a paper you can find it at bioRxiv, at https://www.biorxiv.org/content/early/2018/09/08/411876.
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