Scientists discover how to program DNA at will – Executive Digest

This is a real breakthrough for genetic engineering: a team of researchers from the Arc Institute (USA) has developed a mechanism called “bridge recombinase”, which will become a powerful and extraordinarily accurate tool for scientists to ‘program’ DNA. Comfortable.

The discovery, recently published in the journal ‘Nature’, shows that this programmable ‘DNA bridge’ allows researchers to specify any gene sequence they want, and any DNA molecule they later want to insert into the genome.

“DNA bridging – says the paper’s lead author Patrick Hsu – is a new method for biological programming. ‘Bridge recombinase’ can globally modify genetic material through insertion, excision, sequence-specific inversion and more, enabling a ‘word processor’ for the living genome. .

The ‘recombinase bridge’ comes from elements called insertion sequence 110 (IS110), one of several types of transposable elements, also known as “jumping genes”, that cut and paste to switch positions within and between microbial genomes.

These components are present in all forms of life and have evolved into truly professional DNA manipulation machines that organisms use to survive. IS110 elements are rare and consist of a single gene encoding a recombinase enzyme, as well as a sequence of DNA segments surrounding it, whose function has remained a mystery until now.

In his lab, Hsu found that when IS110 is excised from a gene, the ends of the non-coding DNA come together to form an RNA molecule (an RNA bridge) that folds into two turns. One of these loops binds to the S110 element and the other to the target DNA into which it is inserted. Bridging RNA is the first example of a bispecific guide molecule.

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Each of the two loops of bridging RNA can be programmed independently, so researchers can mix and match any DNA sequence of interest to the target and donor. This means that the IS110 element can go beyond its normal function of insertion and allow the insertion of any genetic payload, such as a functional copy of a defective disease-causing gene, into any part of the genome.

In this work, the team of scientists demonstrated the ability to insert more than 60% of the desired gene into E. coli with more than 94% specificity for the exact gene location.

“These programmable RNA bridges – says Nick Perry, co-author of the study – distinguish IS110 from other known recombinants, which do not contain RNA components and cannot be programmed. The RNA bridge makes IS110 compatible with any outlet, as if it were a universal power adapter.

“This bridging recombination mechanism “addresses some of the most important challenges faced by other genome editing methods: the ability to programmatically rearrange two DNA molecules opens the door to major advances in genome design.”

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