Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)–mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, and intestines with higher efficiency and safety compared to benchmark delivery systems, DLin-MC3-DMA and jetPEI. We demonstrate that LNPs can deliver mRNAs to induce hepatic production of therapeutic secreted proteins. These LNPs may provide a platform for in utero mRNA delivery for protein replacement and gene editing.
We investigated in a sample of Latinos the practices of antimicrobial drug importation and use of nonprescribed antimicrobial drugs. In interviews conducted with 219 adults, we assessed health beliefs and past and present behaviors consistent with acquiring antimicrobial drugs without a prescription in the United States. Many (30.6%) believed that antimicrobial drugs should be available in the United States without a prescription. Furthermore, 16.4% had transported nonprescribed antimicrobial drugs into the United States, and 19.2% had acquired antimicrobial agents in the United States without a prescription. A stepwise logistic regression analysis showed that the best predictors of having acquired nonprescribed antimicrobial drugs in the United States were beliefs and behavior consistent with limited regulations on such drugs. Many persons within the Latino community self-medicate with antimicrobial drugs obtained without a prescription both inside and outside the United States, which adds to the reservoir of antimicrobial drugs in the United States.
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