Gene Therapy

How ‘Jumping Genes’ could Transform Gene Editing

Posted on 5 June 2019

Despite the vast beneficial potential of gene therapy there remain some a few hindrances. Two of the most prevalent being, the inefficiency in which the desired genes are integrated into the host cells genome, and the breaking of the DNA structure to allow the new gene to be inserted in, which increase genome instability, a hallmark of aging.

Transposons are ‘jumping genes’ that can be directly inserted into the genome without the need for double-strand breaks and homology-directed repair, which many genome editing methods, such as CRISPR, depend on.

Two teams have developed variants of CRISPR–transposon systems that can potentially increase efficiency up to 40-60% and precision of insertions up to 95%.

Nuclease-deficient CRISPR-Cas systems (e.g. Cascade) can recognise target DNA using guide RNA but does not cut the DNA. After recognising target sequence, Cascade then binds to a protein (TniQ) that guides the insertion of the transposon into the target site.

Proposed model for RNA-guided DNA integration using the INTEGRATE system. Image Credit: Samuel Sternberg

We can program this CRISPR-transposon system to integrate its genetic payload at virtually any genomic site, and by understanding how it works, we will be able to engineer it to be even more effective

Samuel Sternberg of Columbia University in New York, who leads one of the teams


References

  1. Klompe, S.E., Vo, P.L.H., Halpin-Healy, T.S. et al. Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration. Nature 571, 219–225 (2019). https://doi.org/10.1038/s41586-019-1323-z
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