Move over CRISPR, the retrons are coming:
While the CRISPR-Cas9 gene editing system has become the poster child for innovation in synthetic biology, it has some major limitations. CRISPR-Cas9 can be programmed to find and cut specific pieces of DNA, but editing the DNA to create desired mutations requires tricking the cell into using a new piece of DNA to repair the break. This bait-and-switch can be complicated to orchestrate, and can even be toxic to cells because Cas9 often cuts unintended, off-target sites as well.
Alternative gene editing techniques called recombineering instead perform this bait-and-switch by introducing an alternate piece of DNA while a cell is replicating its genome, efficiently creating genetic mutations without breaking DNA. These methods are simple enough that they can be used in many cells at once to create complex pools of mutations for researchers to study. Figuring out what the effects of those mutations are, however, requires that each mutant be isolated, sequenced, and characterized: a time-consuming and impractical task.
Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) have created a new gene editing tool called Retron Library Recombineering (RLR) that makes this task easier. RLR generates up to millions of mutations simultaneously, and "barcodes" mutant cells so that the entire pool can be screened at once, enabling massive amounts of data to be easily generated and analyzed. The achievement, which has been accomplished in bacterial cells, is described in a recent paper in PNAS.
"RLR enabled us to do something that's impossible to do with CRISPR: we randomly chopped up a bacterial genome, turned those genetic fragments into single-stranded DNA in situ, and used them to screen millions of sequences simultaneously," said co-first author Max Schubert, Ph.D., a postdoc in the lab of Wyss Core Faculty member George Church, Ph.D. "RLR is a simpler, more flexible gene editing tool that can be used for highly multiplexed experiments, which eliminates the toxicity often observed with CRISPR and improves researchers' ability to explore mutations at the genome level."
Journal Reference:
Max G. Schubert, Daniel B. Goodman, Timothy M. Wannier, et al. High-throughput functional variant screens via in vivo production of single-stranded DNA [$], Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.2018181118)
(Score: 2, Insightful) by Anonymous Coward on Thursday June 24 2021, @07:08PM (2 children)
sounds like zombie shit to me, man!
(Score: 2) by Mojibake Tengu on Thursday June 24 2021, @08:06PM (1 child)
You won't beleive it, but Shang Hai Ruilan Bao Hu San Biotech Ltd. is a real thing now:
https://residentevilonly.net/wp-content/uploads/2019/06/3d7ea813632762d0853d6637aeec08fa503dc64e.jpg [residentevilonly.net]
https://19851125.en.made-in-china.com/ [made-in-china.com]
The edge of 太玄 cannot be defined, for it is beyond every aspect of design
(Score: 0) by Anonymous Coward on Friday June 25 2021, @09:56PM
ohh, lordy!
(Score: 0) by Anonymous Coward on Thursday June 24 2021, @08:01PM (1 child)
>> we randomly chopped up a bacterial genome
What could possibly go wrong? At least the lab's not in Wuhan.
(Score: 2) by Beryllium Sphere (r) on Thursday June 24 2021, @09:07PM
Almost nothing is a pathogen. Safety issues are for that minority of viruses and bacteria that can cause disease.
(Score: 0) by Anonymous Coward on Thursday June 24 2021, @10:36PM (4 children)
TFA:
Move over the Wuhan Virus! In the year of our Lord 2021, we are welcoming the Wyss Bacterium!
(Score: 1) by sweettea on Thursday June 24 2021, @10:54PM (2 children)
This is a completely standard way of selecting cells -- there are plasmids to convey resistance to at least three antibiotics, and they're commonly used when inserting another gene. With this, it's completely trivial to select for the cells where the inserted DNA was successfully integrated into the genome -- just throw some of the antibiotic in, everything that didn't take those foreign genes in gets killed. If it were an issue, it'd have shown up by now; it's been a standard practice for the history of gene manipulation.
(Score: 0) by Anonymous Coward on Friday June 25 2021, @12:09AM (1 child)
Indeed.
https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance [who.int]
Oh wait...
Not having planetwide lockdown years also has been a standard practice, and for a fair bit longer than that.
Soil microbes produce a whole lot of natural antibiotics that are not fit for medical use anyway due to human toxicity. Their natural competitors have the corresponding resistance genes. Those things could be used in exactly the same way but with precisely zero extra risks.
(Score: 0) by Anonymous Coward on Monday June 28 2021, @02:09PM
While your first and final points stand, the point about a planetwide lockdown is a red herring as the pandemic was caused by a virus rather than some sort of resistant bacteria.
Not saying pandemics aren't bad, or that creating antibiotic resistant bacteria isn't bad, just that the two aren't actually related in any way other than that they are both medical issues.
(Score: 0) by Anonymous Coward on Friday June 25 2021, @04:28AM
the wuhan virus is obsolete having been superseeded by the indian variant
the battle for virus supremacy continues