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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
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An Adipocyte Cell Culture Model to Study the Impact of Protein and Micro-RNA Modulation on Adipocyte Function
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Nanopartículas lipídicas de ARNm selectivas para adipocitos para la programación celular con análisis de aprendizaje

Autumn Greco1, Leonardo Cheng1, Kailei Ding Goodier2

  • 1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Journal of controlled release : official journal of the Controlled Release Society
|August 30, 2025
PubMed
Resumen
Este resumen es generado por máquina.

Los investigadores optimizaron las nanopartículas de lípidos (LNP) para la entrega específica de ARNm a las células del tejido adiposo blanco (WAT). Este avance mejora la ingeniería adipocítica para las terapias de enfermedades metabólicas.

Palabras clave:
Ingeniería de los adipocitosTransfección preferencial por adipocitosSelección de las fórmulasLas nanopartículas de lípidosAnálisis de aprendizaje automáticoEntrega de ARNm

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Área de la Ciencia:

  • Biotecnología
  • Ingeniería metabólica
  • Terapia génica

Sus antecedentes:

  • El tejido adiposo, particularmente el tejido adiposo blanco (WAT), es vital para el metabolismo energético y la señalización endocrina.
  • WAT es un objetivo clave para las terapias de enfermedades metabólicas debido a sus funciones secretoras y abundancia.
  • La terapia génica ofrece potencial para reprogramar los adipocitos para mejorar el metabolismo energético y la secreción de proteínas.

Objetivo del estudio:

  • Para optimizar las nanopartículas lipídicas de ARN mensajero (ARNm) para la transfección preferencial de los adipocitos.
  • Identificar las características clave que impulsan la selectividad de los adipocitos en la entrega de LNP utilizando el aprendizaje automático.
  • Demostrar la entrega efectiva y selectiva de ARNm mediado por LNP a los adipocitos in vivo.

Principales métodos:

  • Proceso de cribado en varios pasos para optimizar la composición de LNP de ARNm para la transfección de adipocitos.
  • Análisis de aprendizaje automático para determinar los factores que influyen en la selectividad de los adipocitos.
  • Validación in vivo de la entrega de ARNm mediada por LNP en el tejido adiposo.

Principales resultados:

  • Optimización exitosa de los LNP de ARNm para mejorar la transfección preferencial de los adipocitos.
  • Identificación de las características críticas de la LNP que promueven la orientación de los adipocitos.
  • Demostración de la entrega potente y selectiva de ARNm in vivo a los adipocitos.

Conclusiones:

  • La optimización de la composición de LNP es crucial para la transfección eficiente de ARNm en los adipocitos.
  • Esta estrategia proporciona un enfoque prometedor para la ingeniería de los adipocitos.
  • Los hallazgos apoyan aplicaciones terapéuticas dirigidas a enfermedades metabólicas a través de la reprogramación de adipocitos.