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The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Cancer-Critical Genes I: Proto-oncogenes01:33

Cancer-Critical Genes I: Proto-oncogenes

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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
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Video Experimental Relacionado

Updated: Feb 26, 2026

Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells
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Circuitos genéticos sintéticos que se dirigen selectivamente a cánceres impulsados por RAS

Gabriel Valentin Senn1, Leon Nissen1, Yaakov Benenson1

  • 1Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.

eLife
|February 24, 2026
PubMed
Resumen
Este resumen es generado por máquina.

Los circuitos genéticos sintéticos se dirigen con precisión a los oncogenes mutados de la rata sarcoma (RAS) en las células cancerosas. Este enfoque novedoso mejora la selectividad y la expresión de proteínas terapéuticas para un mejor tratamiento del cáncer.

Palabras clave:
sensores RASbioquímicabiología del cáncerexpresión de proteínas dirigidas al cáncerbiología químicahumanocircuitos lógicos de múltiples entradasoncogén de la rata sarcomabiología sintéticacircuitos genéticos sintéticos

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Área de la Ciencia:

  • Oncología
  • Biología Sintética
  • Biología Molecular

Sus antecedentes:

  • El RAS mutado es un oncogén prevalente en cánceres humanos, que impulsa el crecimiento tumoral.
  • Los inhibidores actuales de RAS tienen limitaciones, incluida la especificidad para las mutaciones KRASG12C y la resistencia adquirida.
  • Los circuitos genéticos sintéticos ofrecen una estrategia potencial para la terapia del cáncer dirigida al detectar y responder a señales específicas del cáncer.

Objetivo del estudio:

  • Desarrollar circuitos genéticos sintéticos altamente selectivos para dirigirse a oncogenes RAS mutados.
  • Diseñar circuitos genéticos que puedan integrar múltiples señales de mutación RAS para mejorar la especificidad.
  • Demostrar el potencial terapéutico de estos circuitos en cánceres impulsados por RAS.

Principales métodos:

  • Se diseñaron e implementaron circuitos genéticos sintéticos modulares que incorporan múltiples sensores RAS.
  • Se utilizó modelado computacional para optimizar las interacciones de los componentes del circuito y la expresión de salida.
  • Se adaptaron los circuitos para un rendimiento específico de la línea celular para maximizar la selectividad y ajustar la expresión.
  • Se vincularon los circuitos a la expresión de una proteína terapéutica para la eliminación de células cancerosas.

Principales resultados:

  • Se logró una selectividad sin precedentes en la expresión de proteínas de salida en células con RAS mutado.
  • Se demostró la focalización exitosa de diversas líneas celulares de cáncer impulsadas por RAS.
  • Se validó el potencial terapéutico induciendo una potente eliminación de células cancerosas con RAS mutado.
  • Se mostró la adaptación específica de la línea celular para optimizar el rendimiento del circuito.

Conclusiones:

  • Los circuitos genéticos sintéticos representan una prometedora nueva estrategia terapéutica para los cánceres impulsados por RAS.
  • La combinación de múltiples sensores RAS mejora significativamente la selectividad de las células cancerosas.
  • Este enfoque avanza la aplicación de la biología sintética en oncología para terapias dirigidas contra el cáncer.