The recent approval of a CRISPR-Cas9 therapy for sickle cell disease demonstrates that gene editing tools can do a superb job knocking out genes to cure hereditary disease. But it's still not possible to insert whole genes into the human genome to substitute for defective or deleterious genes.
A new technique that employs a retrotransposon from birds to insert genes into the genome holds more promise for gene therapy, since it inserts genes into a "safe harbor" in the human genome where the insertion won't disrupt essential genes or lead to cancer.
Retrotransposons, or retroelements, are pieces of DNA that, when transcribed to RNA, code for enzymes that copy RNA back into DNA in the genome — a self-serving cycle that clutters the genome with retrotransposon DNA. About 40% of the human genome is made up of this "selfish" new DNA, though most of the genes are disabled, so-called junk DNA.
The new technique, called Precise RNA-mediated INsertion of Transgenes, or PRINT, leverages the ability of some retrotransposons to efficiently insert entire genes into the genome without affecting other genome functions. PRINT would complement the recognized ability of CRISPR-Cas technology to disable genes, make point mutations and insert short segments of DNA.
A description of PRINT, which was developed in the laboratory of Kathleen Collins, a professor of molecular and cell biology at the University of California, Berkeley, will be published Feb. 20 in the journal Nature Biotechnology.