Harnessing A Diverse Collection Of CRISPR-Associated RNA-Guided Nucleases And Proprietary Reverse Transcriptases For Precise Gene Editing

Reverse transcriptase (RT) editing occupies a distinct position in the gene editing modality landscape, enabling precise rewriting of short DNA segments where nuclease-based approaches fall short. But translating that precision into meaningful in vivo editing rates has remained a core challenge. Researchers at ElevateBio mined a database of over 10 billion natural proteins to identify proprietary reverse transcriptases spanning retroviral, retrotransposon, group II intron, and retron families, then paired these with CRISPR-associated RNA-guided nucleases exhibiting broad PAM diversity.

Iterative engineering of both the RT editor and guide RNA architecture drove editing of the liver target Hao1 from under 0.1% to over 70% in primary murine hepatocytes, with in vivo editing exceeding 28%. Explore the full findings to see how the platform's engineering approach translated across in vitro and in vivo models.