Chinese researchers have developed what they believe could be a viable, safer alternative to CRISPR for correcting genetic mutations in humans to treat diseases. The technology is called ‘leveraging endogenous ADAR for Programmable editing of RNA, or LEAPER for short.
CRISPR is commonly associated with the Cas9 enzyme. The CRISPR-Cas9 system includes a guide RNA (gRNA) which guides the Cas9 enzyme to make the edit in the correct place. Unfortunately, while the gRNA mostly binds to the target site, off target effects are possible.
The LEAPER system works in a similar way to another gene editing system, CRISPR-Cas13. Like CRISPR-Cas13, LEAPER targets RNA molecules rather than double stranded DNA. In contrast to CRISPR-Cas13, the LEAPER system does not require a gRNA and neither needs the enzyme component. Only one component is required is called arRNA.
According to the researchers, the simpler system is easier to deliver into cells than CRISPR and is likely to be safer and not produce unwanted cellular immune responses.
The researchers tested the LEAPER system on human cells taken from donors with the genetic disorder Hurler syndrome. Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 – A disease affecting lysosomal storage. The disease causes skeletal abnormalities, heart disease, cognitive impairment, an enlarged spleen and liver and a greatly reduces life expectancy.
Using LEAPER, the scientists were able to correct the genetic mutation that causes the disease in ‘sufficient amounts” of the cells’ mutated RNA to make the system viable a potential treatment for the disease.
The researchers are continuing to work on the new technology and are now moving on to trials on animals. It may be some time before it is known if the LEAPER system is a viable method of correcting genetic mutations in humans and is safer or more effective than CRISPR-Cas9.
The research is detailed in the paper – Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs – which was recently published in the journal Nature Biotechnology. DOI: 10.1038/s41587-019-0178-z