Knockdown of lactate dehydrogenase by adeno-associated virus-delivered CRISPR/Cas9 system alleviates primary hyperoxaluria type 1.

ABSTRACT:

Background

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder caused by endogenous overproduction of hepatic oxalate, leading to hyperoxaluria, recurrent calcium oxalate kidney stones, and end-stage renal disease. Lactate dehydrogenase (LDH) is an ideal target for diminishing oxalate production as it is responsible for glyoxylate to oxalate conversion in the liver, the last step of oxalate metabolism. Here, we investigated the therapeutic efficacy and potential side effects of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology to ameliorate PH1 via specifically disrupting the hepatic LDH.

Methods

Pheochromocytoma (PC12) cells were used to assess the efficacy of cleavage of single-guide RNAs in vitro. PH1 neonatal rats were injected

SUBMITTER: Zheng R 

PROVIDER: S-EPMC7752156 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature