Genome editing in the human liver: Progress and translational considerations

Area of Science:

• Hepatology and Genetic Medicine
• Molecular Biology and Gene Therapy

Background:

• Liver-targeted genome editing presents a promising therapeutic strategy for lifelong benefits after a single treatment.
• It is poised to supersede traditional gene addition methods due to advancements in gene delivery and editing technologies.

Purpose of the Study:

• To explore the potential of liver-targeted genome editing as a therapeutic modality.
• To identify and address the challenges hindering the clinical translation of this technology.

Main Methods:

• Review of current advancements in liver-targeted gene delivery and genome editing techniques.
• Analysis of liver-specific biological factors influencing therapeutic efficacy.
• Examination of strategies for achieving therapeutic editing levels and mitigating off-target effects.

Main Results:

• The liver's unique characteristics make it a prime target for genome editing therapies.
• Successful strategies for achieving genome editing in the liver have been identified.
• Pre-existing immunity to nucleases and achieving in vivo editing efficiency are key hurdles.

Conclusions:

• Liver-targeted genome editing is a feasible and achievable near-term therapeutic approach.
• Overcoming challenges related to editing efficiency, off-target effects, and immune responses is crucial for clinical application.
• Further research and translational considerations are necessary to bring genome editing therapies to the clinic.