TN-501

TN-501 is a one-time adeno-associated virus serotype 9 (AAV9) gene editing therapy developed by Tenaya Therapeutics. It is designed to address PLN-R14del-associated cardiomyopathy, a genetic heart disease caused by a mutation in the Phospholamban (PLN) gene. The therapy aims to specifically inactivate the mutant PLN-R14del allele, thereby eliminating the toxic effects of the mutant protein while preserving the function of the wild-type allele. TN-501 achieves cardiac-specific, transient Cas9 expression without germline editing, employing self-inactivation and liver de-targeting strategies. It utilizes a cardiac-selective human cardiac troponin T promoter (hcTnTp) to drive the expression of Staphylococcus aureus Cas9 (SaCas9) in cardiac tissues, and a human U6 promoter (U6p) to control the expression of a guide RNA (gRNA) optimized for targeting the human PLN-R14del locus.