A Singular Base Editing Platform for Polyfunctional Multiplex Engineering of Immune Cells.

A lipid nanoparticle platform for high yield CRISPR-targeted homology directed repair enables fully non-viral CAR T cell generation

Establishment of a scalable engineered cell-line platform for direct, GMP-grade production of eVLP vectors enabling streamlined generation of gene-edited CAR-T/NK cells

An industrial-grade platform based on monoclonal producer cell lines that enables the continuous and scalable generation of engineered virus-like particles (eVLPs) co-packaging Cas9–gRNA ribonucleoproteins (RNPs) and provides a GMP-compliant and broadly adaptable strategy for the streamlined manufacturing of next-generation autologous and allogeneic gene-edited CAR-T/NK therapies.

Base editing for precision therapeutics.

Key remaining challenges include bystander editing within the activity window, residual off-target DNA and RNA editing, delivery constraints, delivery constraints, immunogenicity, and the need for durable long-term safety evidence across relevant cell types and disease contexts.

Repurposing base editors for targeted knock-in and simultaneous multiplex knockouts to generate allo-CAR T cells with minimal translocations.

Compared with multiplex Cas9 editing, BEKI markedly reduced chromosomal translocations while preserving cell viability, and provides a streamlined and scalable strategy for multiplex CAR T-cell engineering with improved genomic stability, advancing safer next-generation cell therapies for cancer and autoimmune diseases.

Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells.

A virus-like particle (VLP)-based toolkit that delivers diverse CRISPR editing modalities to human monocytes, macrophages and dendritic cells with high efficiency while preserving viability and innate immune responsiveness is presented.

Engineering editopes through programmable RNA editing toward tumor neoantigen generation.

Neoepitope-based therapies hold great promise for cancer immunotherapy because they target tumor-specific mutations and elicit potent anti-tumor T-cell responses. However, their clinical implementation remains limited by the complexity of neoepitope discovery and uncertainty regarding presentation by tumor cells. A potential alternative is the generation of immunogenic neoepitopes directly within cancer cells through programmable RNA editing. Here, we develop Short Precise-Encodable ADAR Recruiting (SPEAR) gRNAs that harness endogenous ADAR1 to direct precise adenosine-to-inosine (A-to-I) editing at selected transcript sites. Using these gRNAs, we demonstrate the generation of immunogenic neoepitopes through RNA editing at the transcript level, termed editopes. In a proof-of-concept model based on the melanoma antigen MART-1, SPEAR-mediated RNA editing restored antigen-specific T cell recognition and enabled tumor control in vivo. Finally, we developed a computational pipeline to identify candidate tumor-selective neoepitopes across multiple cancer types amenable to guided RNA editing. Our findings establish programmable RNA editing as a strategy for engineering immunogenic editopes and provide a framework for neoepitope-directed cancer immunotherapy.