In Vivo Investigation Of RNA Optimization Strategies For Maximizing Gene Editing In The Liver

Optimizing mRNA-based therapeutics requires more than just selecting a target, it demands a coordinated strategy across RNA design, guide chemistry, and delivery platform engineering. This asset explores how internal mRNA modifications, codon and UTR optimization, and guide RNA tuning can significantly enhance editing potency in vivo, even at low doses. Using liver-targeted LNPs and proprietary RNA-guided nucleases, researchers achieved meaningful gene edits in mouse and non-human primate models, with functional outcomes confirmed through biomarker analysis and protein reduction.

The document also highlights the importance of balancing gRNA:mRNA ratios, validating accessory proteins for complex payloads, and leveraging base editors to target disease-relevant genes with high specificity. Safety and tolerability data from NHP studies show minimal transient liver enzyme elevations and no biologically meaningful changes in plasma markers, supporting the clinical potential of these approaches.

For teams working in genomic medicine, this resource offers a comprehensive look at how iterative RNA and delivery optimizations can unlock new therapeutic possibilities. Whether you're developing liver-targeted treatments or exploring base editing for rare diseases, the insights here can help guide your next steps.