Supplementary Material for: Biodistribution of Polymeric Nanoparticles following In-Utero Delivery to a Non-Human Primate

Monogenic diseases can be diagnosed before birth. Systemic fetal administration of nanoparticles (NP)s grants therapeutic access to developing stem cell populations impacted by these classes of disease. Delivery of editing reagents in these NPs administered before birth have yielded encouraging results in preclinical mouse models of monogenic diseases. 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 non-human primates (NHPs) in mid-gestation examining systemic delivery of polymeric NPs loaded with flourescent dye. 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. 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.

单基因疾病可在出生前诊断。纳米颗粒（nanoparticle, NP）的全身性胎儿给药，为受此类疾病影响的发育中干细胞群提供了治疗途径。出生前给药的这些NP中携带的编辑试剂，在单基因疾病的临床前小鼠模型中已取得令人鼓舞的结果。为将该策略转化至临床应用，需在大型动物中验证其安全性与有效性。我们在3只妊娠中期的胎儿非人灵长类动物（non-human primate, NHP）中开展了一项初步生物分布研究，考察负载荧光染料的聚合物纳米颗粒的全身性递送情况。研究发现其分布与小鼠实验结果存在若干相似之处，即胎儿肝脏与脾脏对NP的广泛摄取。一个在小鼠实验中未重现的显著发现是，NP在胎儿骨骼的增殖区与骨化区发生了积累。尤为重要的是，胎儿的雄性或雌性生殖系区域及母体组织中未出现NP积累。这些研究对于下一步在胎儿NHP中测试编辑试剂（以实现出生前治疗单基因疾病的目标）至关重要。