ArticleProceedings of the National Academy of Sciences of the United States of America2024
In utero delivery of targeted ionizable lipid nanoparticles facilitates in vivo gene editing of hematopoietic stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Reappraising the topology of cell-free fetal DNA in maternal blood toward improved prenatal genetic diagnostics.Science advances · 2026Review
- Advancements of mRNA-lipid nanoparticle links to gene editing and immune responses.Journal, genetic engineering & biotechnology · 2026Review
- Preparation of placenta-tropic mRNA lipid nanoparticles for pregnancy disorders.Nature protocols · 2026Review
- Recent Advances in Non-Viral Vectors for Gene Therapy and Gene Delivery: From Lipid Nanoparticles to Engineered Extracellular Vesicles.Pharmaceutics · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- The Nucleolus in Human Disease: Ribosome Biogenesis, Nucleolar Surveillance, and Therapeutic Opportunities.Biomolecules · 2026Review
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Lipid nanoparticle screening in nonhuman primates with minimal loss of life.Nature biotechnology · 2026Article
- miRNA-Mediated Regulation of γ-Globin to β-Globin Switching: Therapeutic Potential in β-Hemoglobinopathies.International journal of molecular sciences · 2026Review
- Review
- Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.International journal of nanomedicine · 2026Review
- Targeted delivery of genome editors in vivo.Nature biotechnology · 2026Review
- Therapeutic nanoparticle safety in pregnancy: Bridging knowledge gaps with environmental insights and a translational roadmap.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Delivering the Message: Translating mRNA Therapy for Liver Inherited Metabolic Diseases.Journal of inherited metabolic disease · 2025Review
- Investigation of the protein corona and biodistribution profile of polymeric nanoparticles for intra-amniotic delivery.Biomaterials · 2025Article
- Article
- Integration of Clinical, Radiographic, Histologic, and Molecular Findings to Diagnose Craniofacial Fibrous Dysplasia.The Journal of craniofacial surgery · 2025Article
- Advancing Cancer Immunotherapy Using Lipid Nanoparticle-Based Approaches.International journal of nanomedicine · 2025Review
- Circular RNAs modulate cancer drug resistance: advances and challenges.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Enhancing nucleic acid delivery by the integration of artificial intelligence into lipid nanoparticle formulation.Frontiers in medical technology · 2025Review
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Authors and funding
25 authors.
Funding
Abstract
Monogenic blood diseases are among the most common genetic disorders worldwide. These diseases result in significant pediatric and adult morbidity, and some can result in death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise to alter the therapeutic landscape but are not without potential limitations. In vivo gene editing therapies offer a potentially safer and more accessible treatment for these diseases but are hindered by a lack of delivery vectors targeting HSCs, which reside in the difficult-to-access bone marrow niche. Here, we propose that this biological barrier can be overcome by taking advantage of HSC residence in the easily accessible liver during fetal development. To facilitate the delivery of gene editing cargo to fetal HSCs, we developed an ionizable lipid nanoparticle (LNP) platform targeting the CD45 receptor on the surface of HSCs. After validating that targeted LNPs improved messenger ribonucleic acid (mRNA) delivery to hematopoietic lineage cells via a CD45-specific mechanism in vitro, we demonstrated that this platform mediated safe, potent, and long-term gene modulation of HSCs in vivo in multiple mouse models. We further optimized this LNP platform in vitro to encapsulate and deliver CRISPR-based nucleic acid cargos. Finally, we showed that optimized and targeted LNPs enhanced gene editing at a proof-of-concept locus in fetal HSCs after a single in utero intravenous injection. By targeting HSCs in vivo during fetal development, our Systematically optimized Targeted Editing Machinery (STEM) LNPs may provide a translatable strategy to treat monogenic blood diseases before birth.
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