Universal donor cells
Patent Information
- Application Number
- JP2025117434
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2020-02-21
- Filing Date
- 2025-07-11
- Publication Date
- 2025-12-17
AI Technical Summary
Existing methods for generating universal donor cells face limitations such as susceptibility to natural killer (NK) cell lysis due to lack of HLA expression and residual mRNA, and potential off-target cleavage issues with TALEN technology, which pose safety concerns for clinical use.
The method involves delivering site-specific nucleases like CRISPR-Cas9 to target genes encoding survival factors (e.g., TXNIP, ZNF143, FOXO1, MANF) and tolerogenic factors (e.g., PD-L1, HLA-E, HLA-G, CTLA-4, CD47) to generate universal donor cells with enhanced immune evasion and survival capabilities, using specific gRNAs to ensure precise gene editing.
The generated universal donor cells demonstrate increased immune evasion and survival post-engraftment by reducing MHC-I expression and introducing tolerogenic factors, thereby overcoming NK cell lysis and allogeneic rejection.