Therapeutic/Technology: Gene-modified, personalized cell therapy
Engineering pluripotent stem cells for universally available, off-the-shelf T cell therapies
Research Objective Our goal is to develop new gene editing methods for producing universal, off-the-shelf, therapeutic T cells from induced pluripotent stem cells (iPSC) that can be applied to a range of diseases. Impact We will develop new gene editing approaches to overcome the block to T cell development from iPSC that occurs when key […]
Phase 2 Study of Hematopoietic Stem Cell Gene Transfer Inducing Fetal Hemoglobin in Sickle Cell Disease
Therapeutic Candidate or Device Autologous CD34+ cells transduced ex vivo with the BCH_BB694 LCR(-HS4) bGp D12shmiR lentiviral vector Indication Sickle cell disease with severe phenotype. Therapeutic Mechanism Silencing of beta-sickle globin and induction of anti-sickling fetal hemoglobin Unmet Medical Need Sickle cell is a severe disease with protean manifestations. The only curative therapy is an […]
Transplantation of CRISPR-CAS9 Corrected Hematopoietic Stem Cells (CRISPR_SCD001) in Patients with Severe Sickle Cell Disease
Therapeutic Candidate or Device CRISPR corrected blood stem cells are manufactured from persons with severe sickle cell disease and returned by transplant to the same person Indication Persons with sickle cell disease (adults and adolescents) with repeated, severe painful and lung events are eligible for the clinical trial Therapeutic Mechanism Blood stem cells are harvested […]
Evaluation of Gene Therapy Approaches for Autosomal Recessive Hyper IgE Syndrome Due to Mutations in DOCK8
Gene-corrected human microglia for the treatment of adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)
Research Objective The research proposed here will support the development of NGL-101, a cell therapy for treating adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Impact Successful development of NGL-101 will result in a life-altering therapy for patients suffering from ALSP and provide proof of concept for treating other microglia diseases. Major Proposed Activities […]
A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells
Research Objective A Treatment for Artemis-deficient Severe Combined Immunodeficiency using Non-Viral CRISPR-driven Safe Harbor Transgenesis in Hematopoietic Stem Cells Impact We aim to develop a novel genome editing based therapy for Artemis-deficient severe combined immunodeficiency that would improve upon prior gene therapies in efficacy, safety, and scalability. Major Proposed Activities Discover optimal approach for nonviral […]
Autologous stem cell-derived interneuron cell therapy for spinal cord injury (SCI)
Research Objective Functional restoration following spinal cord injury using defined excitatory and inhibitory spinal interneuron progenitor cell transplantation Impact The development of a stem cell derived progenitor cell therapy with disease modifying potential for spinal cord injury Major Proposed Activities Define and characterize DI4 GABA and V3 Glut spinal interneuron progenitor cells derived from pluripotent […]
An hematopoietic stem-cell-based approach to treat HIV employing CAR T cells and anti-HIV broadly neutralizing antibodies.
Research Objective We propose to transduce hematopoietic stem cells with vectors that encode chimeric antigen receptors targeting HIV for T cells and anti-HIV broadly neutralizing antibodies for B and/or plasma cells. Impact Recent methods are limited by the rise of escape mutants against a single CAR. Our approach solves this issue by the ability to […]
CAR T cells targeting abnormal N-glycans for the treatment of refractory/metastatic solid cancers
Research Objective Develop genetically modified chimeric antigen receptor T cells to kill incurable solid cancers by targeting a previously un-targetable tumor associated carbohydrate antigen. Impact Refractory/metastatic solid cancers are almost always incurable and have limited therapeutic options. Directing the immune system to kill cancer cells provides an unprecedented new approach. Major Proposed Activities Engineer and […]
Defining the Optimal Gene Therapy Approach of Human Hematopoietic Stem Cells for the Treatment of Dedicator of Cytokinesis 8 (DOCK8) Deficiency
Research Objective A new therapeutic option for DOCK8 deficiency using autologous human hematopoietic stem cells modified through either lentiviral gene addition or CRISPR/Cas9 based gene editing. Impact Allogeneic HSCT is complicated by comorbidities that can be addressed by autologous stem cell gene therapy. This is relevant for DOCK8 deficiency and can be applied broadly to […]