Ionizable drug delivery systems for efficient and selective gene therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Molecular Biology

Background:

• Gene therapy holds promise for treating diseases by correcting abnormal gene function.
• Effective and safe delivery of nucleic acid formulations to target tissues remains a significant challenge.
• Ionizable drug delivery systems (IDDSs) represent a significant advancement, exemplified by COVID-19 vaccines.

Purpose of the Study:

• To systematically classify ionizable drug delivery systems (IDDSs).
• To summarize the characteristics, advantages, and design mechanisms of IDDSs for gene therapy.
• To review the delivery mechanisms and therapeutic applications of IDDSs for various nucleic acids.

Main Methods:

• Classification of existing IDDSs.
• Review of literature on IDDS characteristics, advantages, and design principles.
• Comprehensive analysis of IDDS delivery mechanisms and therapeutic applications for pDNA and RNA molecules.

Main Results:

• IDDSs offer reduced toxicity compared to cationic vectors, enhanced cellular uptake, and improved endosomal escape due to pH-responsive properties.
• The review categorizes IDDSs and details their performance in delivering pDNA and various RNA types.
• Organ-targeting strategies and high-throughput screening methods are highlighted for developing advanced IDDSs.

Conclusions:

• IDDSs are crucial for advancing precise gene therapy by overcoming current delivery challenges.
• Further research into IDDS design mechanisms, organ selection, and high-throughput screening is needed.
• This review provides a foundation for designing next-generation gene vectors with enhanced delivery capabilities.