Beyond Permanent Genome Editing: Molecular Delivery Strategies for RNA Editing and Epigenome-Editing Therapeutics

Area of Science:

• Molecular Biology
• Genetics
• Biotechnology

Background:

• Reversible genetic medicines provide programmable control over RNA and gene expression.
• Unlike permanent genome editing, these therapies avoid irreversible genomic alterations.
• Reversibility encompasses mechanistic, functional, and clinical aspects, not just a binary state.

Purpose of the Study:

• To review reversible genetic medicine technologies, focusing on RNA and epigenome editing.
• To examine various delivery systems and their associated challenges.
• To define criteria for evaluating the success of these therapeutic systems.

Main Methods:

• Systematic review of literature on reversible genetic medicines.
• Analysis of payloads including oligonucleotides, CRISPR-Cas13, and epigenome editors.
• Evaluation of delivery barriers (e.g., degradation, immune response) and clinical factors (e.g., dosing, safety).

Main Results:

• Diverse payloads like ADAR-recruiting oligonucleotides and CRISPR-based editors are discussed.
• Delivery challenges include nuclease degradation, immune recognition, and cellular entry.
• Key considerations for clinical translation include tissue selectivity, duration, safety, and controllability.

Conclusions:

• Effective delivery systems are crucial for reversible genetic medicines.
• Therapeutic success depends on achieving functional editing, controlled duration, and safe reversibility.
• Future development requires addressing manufacturing, quality control, and regulatory pathways.