Engineered lipid nanoparticles for in vivo and durable editing of haematopoietic stem cells within humanized mice.

Click-Chemistry Functionalized Lipid Nanoparticles for In Vitro and In Vivo Transfection of Primary Human CD4+ T Cells.

CD4+ T cells orchestrate adaptive immunity and strategies that enable their genetic reprogramming hold promise for treating cancer, immune dysregulation and infectious diseases such as HIV. However, current T cell engineering approaches rely heavily on ex vivo manipulation, which is labor-intensive, costly, and can alt...

Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease

SUMMARY Ex vivo hematopoietic stem cell (HSC) gene therapy is effective for non-malignant blood disorders including sickle cell disease (SCD), but requires hospitalization, ex vivo cell manipulation, and conditioning. Direct in vivo gene delivery could remove these barriers and widen access. Here, we explore phagocytos...

Optimizing CRISPR/Cas9 genome editing in primary human hematopoietic cells to advance studies into HIV biology

In vivo HSPC gene therapy of hemoglobinopathies without drug selection of corrected cells

In vitro studies in an erythroid progenitor cell line and primary CD34+ cells demonstrated that the EPORW439* variant conferred a strong proliferative advantage to therapeutically modified erythroid progenitors, establishing a strategy to amplify the therapeutic benefit of otherwise limited in vivo HSPC gene editing fo...

Host Barriers to In Vivo HSC Gene Therapy with Helper-Dependent Adenovirus Vectors

Ex vivo hematopoietic stem cell (HSC) gene therapy strategies have proved effective for the treatment of various diseases, with recent advances leading to the clinical approval of several cell products. To overcome issues associated with the cost and technical complexity of ex vivo strategies, we turn towards in vivo s...

Engineering T cells in vivo to express a synthetic cytokine receptor enables preferential expansion and enrichment of anti-CD22 CAR T cells.

Preclinical studies are described demonstrating that UB-VV400 generates anti-CD22 CAR T cells that kill CD22-expressing B cells and tumor cells in vitro and in vivo, and that engagement of RACR results in the selective expansion and enrichment of CAR T cells in vivo leading to complete tumor clearance and B cell deplet...