Biodistribution of Polymeric Nanoparticles following in utero Delivery to a Nonhuman Primate
Year: 2024
Type: article
Abstract: Introduction: Monogenic diseases can be diagnosed before birth. Systemic fetal administration of nanoparticles (NPs) grants therapeutic access to developing stem cell populations impacted by these classes of disease. Delivery of editing reagents in these NPs administered before birth has yielded encouraging results in preclinical mouse models of monogenic diseases. Methods: To translate this strategy clinically, the safety and efficacy of this strategy in larger animals will be necessary. We performed a pilot biodistribution study in 3 fetal nonhuman primates (NHPs) in mid-gestation examining systemic delivery of polymeric NPs loaded with fluorescent dye. Results: We found several similarities in distribution to our experience in mice, namely, extensive uptake in fetal liver and spleen. A striking finding that is not recapitulated in the mouse was the accumulation of NPs in the zones of proliferation and ossification of the fetal bone. Of great importance, there did not appear to be NP accumulation in the fetal male or female germline zones or maternal tissue. Conclusion: These studies were vital to the next step of testing editing reagents in the fetal NHP with a goal of treating monogenic diseases before birth.
Source: Biomedicine Hub
DOI: 10.1159/000543138
Institutions: Yale University, Virscio (United States)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,670
Funders: Yale University, American Surgical Association Foundation, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1044130170, G5520316217, Optimization of Polymeric Nanoparticles Encapsulating Peptide Nucleic Acids for In Utero Gene Editing of the Fetal Brain., Engineering of Polymeric Particles for Fetal Therapy, Yale Clinical and Translational Science Award, Short Term Research Training: Students in Health Professional Schools
OpenAlex ID: W4405350146