sgRNA amount is a limiting factor in adenine base editing using RNA LNPs

Molecular Therapy — Nucleic Acids 2026 Open access

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Authors: Alexandra Birkenshaw, Tyler Thomson, Mai P. Truong, Yui Komaki, Nadine Ramsden, Ana Timpano, Cassie Huang, Anna K. Blakney, Daniel Z. Kurek, Jayesh A. Kulkarni, Colin J.D. Ross
DOI: 10.1016/j.omtn.2026.102909
Cited by: 2
References: 31

Abstract

tissue analysis, and sequencing. Increasing the guide RNA dose to 4 mg/kg enhanced editing efficiency up to 3.3-fold in multiple tissues compared to the standard 1 mg/kg dose, with the liver exhibiting the highest on-target editing rates at 63%. Bystander editing increased significantly with higher guide RNA doses, particularly in highly edited tissues like the liver, where bystander edits showed a dose-dependent increase. These findings demonstrate the importance of careful guide RNA dose optimization to balance editing efficiency and tissue specificity with bystander effects in the therapeutic applications of ABE8e.

Fields of Study & Subjects

RNA regulation and disease CRISPR and Genetic Engineering RNA and protein synthesis mechanisms

Publication details

Journal / source
Molecular Therapy — Nucleic Acids
Publisher
Elsevier BV
Volume
37
Issue
2
Pages
102909–102909
Publication date
18 March 2026
Language
EN