Innovations in Delivering Genome Editing Cargos to Hematopoietic Stem and Progenitor Cells: Vectors, Small Molecules, and Engineering Approaches

Hematopoietic stem and progenitor cells (HSPCs) are prime targets for curative gene therapies, yet they are rare, fragile, and difficult to manipulate without losing long-term repopulating capacity. As genome editing tools (CRISPR–Cas, base editors, prime editors) advance, the key limitation has shifted from editing chemistry to cargo delivery: how to introduce these tools efficiently, safely, and at scale into clinically relevant HSPC subsets. This research topic focuses on innovative delivery strategies—spanning vectors, small molecules, and engineering approaches—to overcome this bottleneck and enable robust, clinically translatable HSPC genome editing.HSPCs underpin durable therapies for inherited and acquired blood and immune diseases, but efficient, precise, and non-toxic delivery of genome editing cargos into these cells remains challenging. This topic welcomes multidisciplinary work on new and improved platforms for delivering nucleases, editors, and repair templates to HSPCs ex vivo (and, where relevant, in vivo), and on how these platforms affect HSPC biology, safety, and therapeutic efficacy.This topic invites contributions in areas such as:Viral and non‑viral vectors for HSPCsDesign and optimization of lentiviral, AAV, virus-like particles, and synthetic nanoparticles for DNA, mRNA, or RNP delivery.Small-molecule enhancers of editingCompounds that tune DNA repair pathways, cell cycle, chromatin state, or innate immune responses to boost editing and preserve stemness.Physical and bioengineering delivery methodsElectroporation, microfluidic and mechanoporation systems, and biomaterial scaffolds tailored to fragile HSPCs.Targeted delivery to true long-term HSCsLigand-, antibody-, or aptamer-based targeting strategies that enrich delivery to long-term repopulating cells.Functional and safety profilingImpact of delivery modality on viability, differentiation, clonal dynamics, off-target effects, and genomic integrity in preclinical models.Translation and manufacturingGMP-compatible, scalable workflows; comparisons of cost, complexity, and regulatory considerations for different delivery platforms.By integrating insights across these domains, this topic aims to accelerate the development of delivery strategies that support safe, precise, and broadly accessible genome editing therapies based on hematopoietic stem and progenitor cells. Topic editors: Srujan Marepally Source: https://www.frontiersin.org/research-topics/76276/innovations-in-delivering-genome-editing-cargos-to-hematopoietic-stem-and-progenitor-cells-vectors-small-molecules-and-engineering-approaches