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Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
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ARCADE: Diseño de códon controlado desde modelos de fundación a través de ingeniería de activación

Jiayi Li1, Litian Liang1, Shiyi Du1

  • 1Ray and Stephanie Lane Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, 15217, US.

bioRxiv : the preprint server for biology
|September 2, 2025
PubMed
Resumen
Este resumen es generado por máquina.

ARCADE ofrece un control flexible sobre el diseño de secuencias de codones de ARNm mediante el uso de ingeniería de activación y modelos genómicos previamente entrenados. Este enfoque mejora el diseño de secuencias biológicas programables para aplicaciones como vacunas de ARNm y terapias de edición de genes.

Palabras clave:
ingeniería de activacióngeneración de secuencia controlablemodelo de fundación para la genómicaFormación posterior en el modelo de fundaciónDiseño del ARNm

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Área de la Ciencia:

  • La bioinformática
  • Biología computacional
  • Biología sintética

Sus antecedentes:

  • El diseño de la secuencia de codón es esencial para la terapia de ARNm y la edición de genes.
  • Los métodos actuales carecen de la flexibilidad y el control necesarios para diversos objetivos de diseño.

Objetivo del estudio:

  • Introducir ARCADE, un nuevo marco para la generación de secuencias de codones flexibles y controlables.
  • Extender la ingeniería de activación a las métricas biológicas continuas para mejorar el diseño de secuencias.

Principales métodos:

  • ARCADE utiliza la ingeniería de activación con modelos de fundación genómica previamente entrenados.
  • Emplea vectores de dirección semánticos biológicamente significativos en el espacio de activación del modelo.
  • El marco modula las propiedades continuas como el índice de adaptación del codón, la energía libre mínima y el contenido de GC sin reentrenamiento.

Principales resultados:

  • ARCADE demuestra un rendimiento superior y una flexibilidad significativamente mayor en comparación con los métodos existentes.
  • El enfoque permite un control preciso sobre múltiples métricas biológicas continuas.

Conclusiones:

  • ARCADE representa un avance significativo en el diseño de secuencias biológicas programables.
  • El marco tiene el potencial de acelerar el desarrollo de nuevas vacunas de ARNm y terapias de edición génica.