Recent Advances in Gene Editing Cargo Delivery for Hematopoietic Stem and Progenitor Cells

As the cornerstone of human hematopoiesis, hematopoietic stem and progenitor cells (HSPCs) sustain immune homeostasis by continuously generating blood cellular components. Their proliferative capacity and multilineage differentiation potential make them prime targets for gene therapy. The clinical application of HSPC genome editing relies on two key advancements: the development of highly specific and biocompatible genome-editing reagents and the establishment of efficient delivery systems ensuring targeted cellular uptake. Recent innovations in gene editing tools and cargo delivery methods, such as RNA- and protein-based editors, have enabled novel therapeutic strategies for hematological disorders. Current gene delivery platforms for HSPCs include electroporation, synthetic nanoscale carriers (e.g., polymeric and lipid nanoparticles), and engineered viral vectors such as integration-defective lentiviral vectors (IDLVs), adeno-associated viral vectors (AADVs), virus-like particles, and adenovirus vectors (AdVs). While ex vivo gene therapy remain predominant, it requires complex and costly patient conditioning regimens. in vivo approaches, primarily utilizing AdVs and LNPs, offer an alternative but lack sufficient targeting precision and transfection efficiency. By critically analyzing these advancements, this review aims to identify pathways for optimizing genome editing in HSPCs and enhancing therapeutic precision in hematological disorder management.