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La proteína similar al retrovirus de mamíferos PEG10 empaqueta su propio ARNm y puede ser pseudotipada para la
Michael Segel1,2,3,4,5, Blake Lash1,2,3,4,5, Jingwei Song1,2,3,4,5
1Howard Hughes Medical Institute, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|August 20, 2021
Resumen
Los científicos rediseñaron un gen viral, PEG10, para empaquetar y entregar ARN específicos utilizando un nuevo sistema llamado encapsidación endógena selectiva para la entrega celular (SEND). Esto ofrece una nueva plataforma para la entrega de ARN terapéutico.
Área de la Ciencia:
- La genómica
- Biología molecular
- Virología
Sus antecedentes:
- Los genomas eucariotas albergan genes virales domesticados, incluidos los homólogos Gag de retrotransposones y retrovirus.
- Los genomas de los mamíferos contienen homólogos de Gag que se ensamblan en partículas similares a los virus.
Objetivo del estudio:
- Investigar la función de los homólogos de Gag de los mamíferos, específicamente el PEG10.
- Desarrollar un nuevo sistema de entrega de ARN basado en las propiedades de PEG10.
Principales métodos:
- Homólogos Gag de mamíferos identificados, incluido el homólogo del retrotransposón LTR PEG10.
- Caracterizada por la capacidad de PEG10 para unirse y secretar su propio ARNm.
- PEG10 de ratón y humano diseñado para empaquetar y entregar ARN específicos, creando el sistema SEND.
Principales resultados:
- PEG10 se une preferentemente y facilita la secreción vesicular de su ARNm.
- La carga de ARNm de PEG10 puede ser reprogramada utilizando sus regiones no traducidas.
- Desarrolló la plataforma SEND para el envasado, la secreción y la entrega de ARN específicos en células de ratón y humanas.
Conclusiones:
- Las capacidades de envasado y secreción de ARNm de PEG10 son reprogramables.
- El sistema SEND representa una plataforma modular y eficiente para la administración de ARN terapéutico.
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