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Image Credit: Bioengineer

Efficient Mitochondrial A-to-G Base Editors Developed

  • Scientists have developed a new generation of mitochondrial DNA base editors that are significantly more efficient and precise compared to previous versions.
  • These enhanced TadA-8e-based adenine base editors demonstrate increased editing activity and an expanded range of editable sequence contexts within mitochondria.
  • Mitochondria, crucial for energy production, have been challenging to manipulate due to low editing efficiency and limited targeting capabilities.
  • The engineered eTd-mtABEs exhibit editing efficiencies of up to 87% in human cellular models, marking a significant advancement in mitochondrial genome engineering.
  • These editors show exceptional specificity, minimizing off-target effects at both DNA and RNA levels, crucial for safe and precise therapeutic applications.
  • The eTd-mtABEs utilize DNA nickases for strand-selective editing, enhancing efficiency and reducing the risk of deleterious double-stranded DNA breaks.
  • In vivo studies in rat models demonstrate editing efficiencies up to 145 times higher than previous editing tools, making them a premier platform for mitochondrial genome manipulation.
  • Researchers successfully generated heritable mitochondrial disease models in rats using these editors, showcasing their potential in exploring disease mechanisms and therapeutics.
  • The innovation in eTd-mtABEs strikes a balance between editing efficiency and specificity, crucial for future therapeutic advancements in mitochondrial gene editing.
  • This breakthrough opens avenues for precise correction of pathogenic mitochondrial variants, potentially revolutionizing the treatment of mitochondrial diseases.

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