Engineering challenges and translational opportunities in emerging gene delivery platforms

Area of Science:

• Biotechnology
• Molecular Biology
• Gene Therapy

Background:

• Clinical gene therapy requires advanced delivery platforms for precise, efficient, and tissue-specific in vivo genetic payload administration.
• Various viral, non-viral, synthetic, and natural vectors have been investigated to meet this need.
• Adeno-associated viruses, lipid nanoparticles, and extracellular vesicles are prominent candidates with unique benefits and challenges.

Purpose of the Study:

• To provide a comparative analysis of leading gene delivery platforms: adeno-associated viruses, lipid nanoparticles, and extracellular vesicles.
• To highlight their design principles, targeting abilities, immunogenicity, and clinical advancement.
• To explore tailoring these platforms for diverse therapeutic applications and disease contexts.

Main Methods:

• Comparative analysis of viral, non-viral, synthetic, and natural gene delivery vectors.
• Survey of preclinical and clinical delivery strategies.
• Evaluation of design principles, targeting capabilities, immunogenicity, and clinical progress of key platforms.

Main Results:

• Adeno-associated viruses, lipid nanoparticles, and extracellular vesicles exhibit distinct advantages and translational hurdles.
• These platforms can be customized for gene therapeutics across various diseases.
• Current limitations and emerging strategies for next-generation gene delivery platforms are identified.

Conclusions:

• Optimizing gene delivery platforms is crucial for advancing clinical gene therapy.
• A comparative understanding of leading vectors informs rational design for improved safety, scalability, and precision.
• Future directions focus on developing next-generation platforms that integrate these critical attributes for broader therapeutic impact.