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Proteínas efectoras de ARN guiadas por ARN programables construidas a partir de partes humanas

Simone Rauch¹, Emily He², Michael Srienc³

¹Department of Chemistry, The University of Chicago, Chicago, Illinois, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.

|June 25, 2019

Resumen

Los investigadores desarrollaron un sistema de orientación de ARN inspirado en CRISPR-Cas (CIRTS) para la manipulación de ARN programable. Este nuevo sistema entrega varias proteínas efectoras para apuntar a transcripciones específicas, ofreciendo nuevas estrategias terapéuticas.

Área de la Ciencia:

Biología molecular
Biología del ARN
Regulación genética

Sus antecedentes:

La regulación epitranscriptómica es crucial para el flujo de información celular.
La orientación de ARN específicos con proteínas efectoras es limitada, lo que dificulta la investigación y las terapias.

Objetivo del estudio:

Desarrollar un nuevo sistema programable para dirigirse a moléculas específicas de ARN.
Para permitir una manipulación precisa de los procesos celulares a nivel de ARN.

Principales métodos:

Estrategia de ingeniería de proteínas para crear un sistema de orientación de ARN inspirado en CRISPR-Cas (CIRTS).
Demostrar la capacidad del CIRTS para suministrar diversas proteínas efectoras (nucleasas, mecanismos de degradación, activadores y editores de bases).

Principales resultados:

CIRTS es un enfoque de orientación de ARN simple y generalizable.
CIRTS es más pequeño que los sistemas de unión de ARN CRISPR-Cas existentes.
El CIRTS puede construirse utilizando componentes de proteínas humanas.

Conclusiones:

CIRTS ofrece una plataforma versátil para el estudio de los procesos reguladores del ARN.
Los CIRTS derivados de humanos pueden mitigar las respuestas inmunes en las terapias de modulación del epitranscriptoma.

Palabras clave:

Regulación del ARN El epitranscriptoma Terapia genética CRISPR humanizado Biología sintética

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