LEAPER (leveraging endogenous ADAR for programmable editing of RNA) is a method of targeted RNA editing that uses short engineered ADAR-recruiting RNAs (arRNAs) to recruit adenosine deaminases ADAR1 and ADAR2 to a specific site to change adenosine to inosine. arRNAa are short stretches of RNA that are partially complementary to the target transcript. The system can be used to correct G (guanosine) to A (adenosine) mutations. During translation of the edited RNA, inosine is thought to be read by translation machinery as guanosine. LEAPER is single molecule system delivered by plasmid, viral vector, or synthetic oligonucleotide and was reported to achieve 80% efficiency with high specificity. The system was shown to restore the activity of α-L-iduronidase in Hurler syndrome patient-derived primary fibroblasts and repair a cancer relevant mutation in TP53 in a HEK293T cell line. Analysis of immune system related markers suggested that LEAPER did not trigger innate immune responses in the cell line.
LEAPER technology was developed by researchers at University of Peking, Beijing and biotechnology company EdiGene. EdiGene is developing therapies based on LEAPER technology to treat Hurler Syndrome and solid tumor treatments.
