LNP-mediated in vivo base editing corrects Agxt to cure primary hyperoxaluria type 1.

ABSTRACT:

Objective

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder caused by AGXT mutations, leading to hepatic oxalate overproduction, nephrolithiasis, and progressive renal failure. This study aims to evaluate the therapeutic potential of base editors delivered via lipid nanoparticles (LNPs) for treating PH1.

Methods

We utilized LNPs to deliver the base editor variant spG-ABE8e into a PH1 rat model. A single-dose injection of LNP-ABE was administered to assess its efficacy in correcting the pathogenic Agxt point mutation.

Results

Treatment with LNP-ABE achieved highly efficient correction of the Agxt mutation, which resulted in the normalization of urinary oxalate excretion, prevention of calcium oxalate deposits, and reversal of renal injury-associ

SUBMITTER: Zhang D 

PROVIDER: S-EPMC12640612 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature