Recent Advances in Gene Therapy for Familial Hypercholesterolemia: An Update Review

Area of Science:

• Cardiovascular Genetics
• Molecular Therapeutics
• Biotechnology

Background:

• Familial hypercholesterolemia (FH) presents significant challenges for existing lipid-lowering therapies, particularly in homozygous cases.
• Achieving target lipid levels remains difficult for many FH patients.
• Novel therapeutic approaches are urgently needed.

Purpose of the Study:

• To review recent advancements in gene therapy for familial hypercholesterolemia.
• To assess the potential of emerging gene therapy vectors and RNA-targeted drugs.
• To explore the future prospects of gene editing for FH treatment.

Main Methods:

• A comprehensive literature search was conducted in PubMed and Clinical Trials databases.
• Studies published between 2018 and 2022 focusing on "Familial hypercholesterolemia" and "Gene Therapy" were selected.
• Data on gene therapy vectors, RNA-targeted drugs, and gene editing technologies were analyzed.

Main Results:

• Optimized adeno-associated viruses, exosomes, and lipid nanoparticles show improved safety and transfection efficiency.
• Numerous RNA-targeted therapies (siRNA, ASO) are in clinical trials, demonstrating significant lipid-lowering effects.
• Gene editing technologies like CRISPR-Cas9 have shown lasting lipid-lowering effects in animal models, suggesting potential for a permanent cure.

Conclusions:

• Gene therapy demonstrates considerable promise for the lipid-lowering treatment of FH.
• Current gene therapy approaches require optimization in terms of delivery efficiency, cost, immunogenicity, and precision.
• Gene editing holds the potential for a definitive cure for FH in the future.