What is the clinical evidence from this study?

Study design: Review. Population: Lipoprotein disorders. Intervention: Gene therapy and genome editing.

What question did this study set out to answer?

This review aims to evaluate the potential of gene therapy and genome editing in treating lipoprotein disorders associated with ASCVD.

April 20, 2026Open Access

Gene therapy and genome editing for lipoprotein disorders

Key Result

Gene therapy and genome editing technologies, such as CRISPR base editing, offer potentially transformative single-course treatments for lipoprotein disorders by permanently inactivating cholesterol-raising genes.

Key Points

This review aims to evaluate the potential of gene therapy and genome editing in treating lipoprotein disorders associated with ASCVD.
Discusses major monogenic and polygenic disorders of lipoprotein metabolism.
Examines RNA-based, gene addition, and gene editing therapies such as CRISPR, and base editing.
Integrates machine learning for risk prediction and polygenic risk scores for risk stratification.
Gene-based therapies show promise in providing durable treatments, potentially reducing reliance on lifelong lipid-lowering therapies.
Personalized approaches using polygenic risk scores can enhance risk assessment and management strategies for lipoprotein disorders.

Structured PICO

Population

Patients with monogenic and polygenic disorders of lipoprotein metabolism, including familial hypercholesterolemia, elevated lipoprotein(a), and familial chylomicronemia syndrome

Intervention

Gene therapy and genome editing (including RNA-based therapies, gene addition, CRISPR, and base editing)

Gene therapy and genome editing represent a promising frontier for the durable management of lipoprotein disorders, potentially revolutionizing ASCVD prevention by addressing the limitations of lifelong traditional lipid-lowering therapies.

Limitations

Immune responses to AAV vectors
Need for precise vector targeting
High cost of therapy
Long-term durability of AAV vector-induced gene expression
Potential off-target effects

Abstract

Genetic factors play a critical role in the development of lipoprotein disorders, which significantly contribute to atherosclerotic cardiovascular disease (ASCVD). Traditional management of these conditions has relied on lipid-lowering therapies, which require lifelong adherence. Recent advancements in gene addition and editing technologies offer novel and potentially transformative approaches for treating lipoprotein disorders by targeting the relevant genetic pathways for each disease. This review revisits major monogenic and polygenic disorders of lipoprotein metabolism, including familial hypercholesterolemia, elevated lipoprotein(a), and familial chylomicronemia syndrome, and discusses the genetic-based therapies for management. RNA-based, gene addition and gene editing therapies, including Clustered Regularly Interspaced Short Palindromic Repeats, base editing and interventions whereby, are highlighted for their potential to provide durable treatments which overcome the adherence challenge. Integration of machine learning for risk prediction and the use of polygenic risk scores to enhance risk stratification further demonstrate the promise of personalized approaches, and overall potential for gene-based treatments to revolutionize ASCVD prevention and management.