Treating Transthyretin Amyloidosis via Adeno-Associated Virus Vector Delivery of Meganucleases.

ABSTRACT: Transthyretin amyloidosis (ATTR) is a progressive and fatal disease caused by transthyretin (TTR) amyloid fibril accumulation in tissues, which disrupts organ function. As the TTR protein is primarily synthesized by the liver, liver transplantation can cure familial ATTR but is not an option for the predominant age-related wild-type ATTR. Approved treatment approaches include TTR stabilizers and an RNA-interference therapeutic, but these require regular re-administration. Gene editing could represent an effective one-time treatment. We evaluated adeno-associated virus (AAV) vector-delivered, gene-editing meganucleases to reduce TTR levels. We used engineered meganucleases targeting two different sites within the TTR gene. AAV vectors expressing TTR meganuclease transgenes were first

SUBMITTER: Greig JA 

PROVIDER: S-EPMC9700363 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature