10033905Developing Genome Editing-induced Gene Silencing (GEiGS) for allogeneic human cell therapiesClosedCollaborative R&DInnovate UKCell therapy involves injecting, grafting, or implanting healthy cells into a patient to repair damaged tissue and/or cells, or to kill tumour cells. Currently, three cell therapies are NICE approved, as a treatment for blood malignancies (Kymriah, Yescarta, Tecartus), with many more in clinical evaluation. Human cell therapy may be allogeneic (nonself/donor-derived) or autologous (self-derived). Allogeneic cell therapy is attractive because a single cell source can be used to treat multiple patients and diverse diseases. This enables manufacture at scale, significantly reducing per-patient treatment costs. In contrast, autologous, _ex vivo_-modified cell therapy is processed in individual batches for the patient being treated, making it expensive and difficult to scale. However, allogeneic cell therapy suffers from the significant drawback of eliciting a significant immune response from the patient, leading to immune rejection. This can be a major issue, requiring costly immunosuppressive therapy, which is often associated with serious and long-term side effects. State-of-the-art gene editing (GE) technologies attempt to reduce the immune response associated with the introduction of allogeneic cells. Human leukocyte antigen (HLA) is the main cause of immune-incompatibility. HLA genes encode the major histocompatibility complex (MHC) membrane-bound glycoproteins in humans. Through GE (e.g., CRISPR/Cas9 gene knockout), HLA proteins can be readily eliminated. However, this creates additional problems since the immune system can detect the lack of HLA expression on target cells, then deploying Natural Killer (NK) cells to attack HLA deficient grafts, unless other 'tolerizing' transgenes are expressed to suppress their activation, an approach which adds further complexity. Skylark Therapeutics has an exclusive licence agreement with Tropic Biosciences to develop their proprietary and patented cutting-edge gene silencing technology (GEiGS) in human therapeutics. GEiGS is a platform technology, which is already proven in plants and animals, but has yet to be fully tested in humans, although its core components (GE and RNA interference - RNAi) are already used as separate modalities in human therapies. GEiGS combines the strengths of both GE and RNAi approaches to deliver stable, tunable, and programmable gene expression regulation. GEiGS is uniquely suited to engineer cells that evade both T and NK cell responses after transplantation, and will therefore enable us to generate allogeneic cell therapies that are not rejected. GEiGS technology has the potential to revolutionise cell therapy, unlocking effective and accessible treatments for a wide range of diseases, including cancers, musculoskeletal disorders, and central nervous system disorders.