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Retron genome editing approach is faster and easier than CRISPR

10 May 2021
Appeared in BioNews 1094

A new genome editing approach may be faster and simpler than CRISPR.

Developed by researchers from the Wyss Institute at Harvard University and Harvard Medical School, Massachusetts, 'retron library recombineering' (RLR) is able to make edits at a large scale without having to cut existing DNA. It can also 'barcode' the changes to allow researchers to easily confirm where the edits were made in multiple cells at once. 

'RLR is a simpler, more flexible gene-editing tool... which eliminates the toxicity often observed with CRISPR and improves researchers' ability to explore mutations at the genome level,' said co-first author Dr Max Schubert.

Retrons are bacterial DNA sequences that generate pieces of single-stranded DNA (ssDNA), and like CRISPR they are part of a bacterial defence mechanism against viruses. 

Where CRISPR/Cas9 works by cutting existing DNA – and risks making edits in the wrong place – RLR introduces the edits to cells as they replicate. The retron produces a piece of ssDNA which – in the presence of an enzyme called single-stranded annealing protein (SSAP) – will be integrated into the DNA of a cell as it divides, so both daughter cells will contain the new sequence. 

Researchers are then able to check that the editing was successful by sequencing for these segments instead of the entire genome.

'Retrons should give us the ability to produce ssDNA within the cells we want to edit rather than trying to force them into the cell from the outside, and without damaging the native DNA, which were both very compelling qualities,' said co-first author Dr Daniel Goodman.

Currently RLR genome editing has only been demonstrated in bacteria, but senior author Professor George Church said 'This work helps us establish a road map toward using RLR in other genetic systems, which opens up many exciting possibilities for future genetic research.'

Harvard gene-editing tool 'sneaks' DNA into cells without making cuts
New Atlas |  3 May 2021
High-throughput functional variant screens via in vivo production of single-stranded DNA
PNAS |  4 May 2021
Move over CRISPR, the retrons are coming
Wyss Institute |  30 April 2021
Retrons display genome editing strengths even CRISPR might envy
Genetic Engineering and Biotechnology News |  30 April 2021
Scientists have created a new gene-editing tool that could outperform CRISPR
Interesting Engineering |  3 May 2021
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