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Nanopartículas de lípidos ionizables para el suministro de ARNm en vivo a la placenta durante el embarazo

Kelsey L Swingle¹, Hannah C Safford¹, Hannah C Geisler¹

¹Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

Journal of the American Chemical Society

|February 15, 2023

Resumen

Los investigadores desarrollaron nuevas nanopartículas lipídicas ionizables (LNP) para la entrega de ARNm a la placenta. Estos LNP diseñados promovieron con éxito la vasodilatación placentaria, ofreciendo un nuevo enfoque terapéutico para los trastornos del embarazo.

Área de la Ciencia:

Ingeniería biomédica
Obstetricia y ginecología
La medicina molecular

Sus antecedentes:

Las nanopartículas lipídicas ionizables (LNP) son vectores no virales avanzados para la entrega de ARNm.
Las aplicaciones existentes de LNP incluyen vacunas y edición de genes, pero no insuficiencia placentaria.
La insuficiencia placentaria afecta la salud materna y fetal debido a un flujo sanguíneo placentario deficiente.

Objetivo del estudio:

Para diseñar LNPs ionizables para la entrega de ARNm dirigida a la placenta.
Investigar las LNP para el tratamiento de la insuficiencia placentaria mediante la promoción de la vasodilatación.
Explorar el potencial del ARNm-LNP para la terapia de reemplazo de proteínas en el embarazo.

Principales métodos:

Formuló una biblioteca de lípidos ionizables para crear LNP para la entrega de ARNm placentario.
Se identificó una formulación de plomo LNP con entrega efectiva in vivo a las células placentarias.
Se ha administrado el ARNm VEGF-A utilizando el LNP principal para evaluar la vasodilatación placentaria.

Principales resultados:

Desarrolló un LNP capaz de entregar ARNm in vivo a los trofoblastos, las células endoteliales y inmunes en la placenta.
La formulación principal de LNP entregó con éxito el ARNm VEGF-A.
La administración de VEGF-A a través de LNP indujo una vasodilatación placentaria significativa.

Conclusiones:

Los LNP ionizables diseñados son prometedores para la entrega de ARNm placentario.
Esta plataforma LNP puede mediar la vasodilatación placentaria, abordando la insuficiencia placentaria.
Los mRNA-LNP representan una estrategia terapéutica potencial para los trastornos placentarios relacionados con el embarazo.

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