Modular lipid nanoparticle delivery of base editor components enables versatile platform strategies for therapeutic genome editing

Developing base editing strategies for therapeutic applications requires more than efficient editing. Delivery must also be flexible enough to support different cell types, editor configurations, and manufacturing approaches while maintaining cell viability and function.

In this ASGCT 2026 poster, Revvity demonstrates how the modular architecture of the Pin-point™ base editing platform can be combined with lipid nanoparticle (LNP) delivery to enable flexible delivery of base editor RNA components to primary human hematopoietic stem and progenitor cells (HSPCs) and T cells.

Because the Pin-point platform separates the nickase, sgRNA, and deaminase into independent components, individual RNAs can be delivered either in separate LNPs or co-encapsulated within a single LNP formulation. This flexibility creates opportunities to tune editor activity and potentially support component-level manufacturing and reuse across therapeutic programs.

The study also demonstrates how modular editor configuration can be used to tune editing outcomes. By selecting deaminase modules with different intrinsic activities or adjusting deaminase expression levels, editing efficiency and bystander activity can be modulated according to the requirements of the target.

Key findings:

• Efficient, high-purity C>T and A>G base editing demonstrated across multiple targets in primary human HSPCs and T cells
• A single A>G conversion at the HBG promoter was sufficient for efficient upregulation of fetal hemoglobin
• Editing outcomes can be tuned by selecting deaminase modules with different activities or adjusting deaminase expression levels
• Modular base editor RNA components can be efficiently delivered to primary HSPCs and T cells using LNPs
• Both individually encapsulated and co-encapsulated LNP formulations achieved efficient editing while maintaining viable cell recovery
• In HSPCs, >60% A>G conversion was achieved without impacting viable cell recovery or the distribution of HSPC subsets
• In T cells, >80% A>G conversion was achieved without impacting viable cell recovery
• Modular architecture enables both independent and co-encapsulation of base editor components, providing flexibility for therapeutic development and manufacturing strategies

The >60% and >80% values, as well as the lack of impact on viable cell recovery, come directly from the poster data. The four main takeaways also align directly with the poster's own summary.

The Pin-point™ base editing platform technology is available for clinical or diagnostic study and commercialization under a commercial license from Revvity.