Hijack of CRISPR defences by selfish genes holds clinical promise

Interesting new article on an E. coli transposon that uses CRISPR to insert itself in bacterial genomes.

Here’s the popular write up:

Hijack of CRISPR defences by selfish genes holds clinical promise

Here’s the actual paper (paywalled):

Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration


The work will inspire researchers working on an entirely different scientific front: the genetic engineering of humans to treat disease. Therapeutic genes are conventionally installed in humans using viruses that either persist outside the cell’s genome (which means that they are rapidly diluted when the cell divides) or land semi-randomly within the genomic DNA (which raises potential safety concerns)7. One solution to this problem is the technique called genome editing8,9 — in which an engineered nuclease, such as Cas9, is targeted to cut DNA at a position of interest to produce a double-strand break (DSB), which is then repaired using a template that facilitates the insertion of a gene at that position10 (Fig. 1a).

Although DSB-driven gene addition is useful, it has limitations. First, it works relatively inefficiently in non-dividing cells, many of which are potential targets for gene therapy. Second, the gene to be inserted must be flanked by DNA segments that match the sequence in the region of the genome into which it is being inserted, which takes up valuable space in the therapeutic agent. And third, the generation of a DSB has an associated risk11, albeit a manageable one. Both Peters et al .6 and Klompe et al . suggest that the reported transposons provide, in principle, a solution to all those issues: the transposon integration process does not require a DSB at the target (Fig. 1b), or flanking DNA in the therapeutic agent, and should work in non-dividing cells. Hence, it could be an attractive approach for human gene editing in the clinic.