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.
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| http://dx.doi.org/10.1159/000543138 | DOI Listing |
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