Gene transfer and genome editing for familial hypercholesterolemia

Canepari, Cesare; Cantore, Alessio

doi:10.3389/fmmed.2023.1140997

Cited by 3 publications

(1 citation statement)

References 150 publications

(186 reference statements)

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“…Nonetheless, satisfactory results have yet to be acquired. Potential barriers of these methods are the gene delivery system itself, immune response, persistence of genes and the possibility of these systems to reach their respective targets 90,91 (Table 1).…”

Section: Gene Therapiesmentioning

confidence: 99%

A narrative review of treatment modalities for familial hypercholesterolemia

Samprokatsidis,

Antza,

Frangou

et al. 2023

JAPT

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Familial Hypercholesterolemia (FH), a commonly missed disorder in a patient with abnormalities in lipid metabolism is described as a heritable disorder presenting elevated LDL cholesterol and lipid deposition in various tissues. This contributes to the early development of manifestations of atherosclerotic disease with the preterm occurrence of severe cardiovascular events. Apparently, decision-making is a strenuous effort and many individuals are underdiagnosed. FH affects LDL receptor and its function plays a critical role in the mechanism of many therapeutic modalities, thus alternative pathways must also be considered. This review addresses the main options of care in individuals with familial hypercholesterolemia along with unconventional drugs like mipomersen, inclisiran, lomitapide, gamcabene, and ANGLT3 inhibitors which have yielded important results for disease management.

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Section: Gene Therapiesmentioning

confidence: 99%

A narrative review of treatment modalities for familial hypercholesterolemia

Samprokatsidis,

Antza,

Frangou

et al. 2023

JAPT

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Advances in nucleic acid-targeted therapies for cardiovascular disease prevention

Makhmudova,

Steinhagen-Thiessen,

Volpe

et al. 2024

Cardiovascular Research

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Nucleic acid-based therapies are being rapidly developed for prevention and management of cardiovascular diseases (CVD). Remarkable advancements have been achieved in the delivery, safety, and effectiveness of these therapeutics in the past decade. These therapies can also modulate therapeutic targets that cannot be sufficiently addressed using traditional drugs or antibodies. Among the nucleic acid-targeted therapeutics under development for CVD prevention are RNA-targeted approaches, including antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and novel genome editing techniques. Genetic studies have identified potential therapeutic targets that are suggested to play a causative role in development and progression of CVD. RNA- and DNA-targeted therapeutics can be particularly well delivered to the liver, where atherogenic lipoproteins and angiotensinogen (AGT) are produced. Current targets in lipid metabolism include proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein A (ApoA), apolipoprotein C3 (ApoC3), angiopoietin-like 3 (ANGPTL3). Several large-scale clinical development programs for nucleic acid-targeted therapies in cardiovascular prevention are under way, which may also be attractive from a therapy adherence point of view, given the long action of these therapeutics. In addition to genome editing, the concept of gene transfer is presently under assessment in preclinical and clinical investigations as a potential approach for addressing low-density lipoprotein receptor deficiency. Furthermore, ongoing research is exploring the use of RNA-targeted therapies to treat arterial hypertension by reducing hepatic angiotensinogen (AGT) production. This review summarizes the rapid translation of siRNA and ASO therapeutics as well as gene editing into clinical studies to treat dyslipidemia and arterial hypertension for CVD prevention. It also outlines potential innovative therapeutic options that are likely relevant to the future of cardiovascular medicine.

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In vivo liver targeted genome editing as therapeutic approach: progresses and challenges

Simoni,

Barbon,

Muro

et al. 2024

Front. Genome Ed.

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The liver is an essential organ of the body that performs several vital functions, including the metabolism of biomolecules, foreign substances, and toxins, and the production of plasma proteins, such as coagulation factors. There are hundreds of genetic disorders affecting liver functions and, for many of them, the only curative option is orthotopic liver transplantation, which nevertheless entails many risks and long-term complications. Some peculiar features of the liver, such as its large blood flow supply and the tolerogenic immune environment, make it an attractive target for in vivo gene therapy approaches. In recent years, several genome-editing tools mainly based on the clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR-Cas9) system have been successfully exploited in the context of liver-directed preclinical or clinical therapeutic applications. These include gene knock-out, knock-in, activation, interference, or base and prime editing approaches. Despite many achievements, important challenges still need to be addressed to broaden clinical applications, such as the optimization of the delivery methods, the improvement of the editing efficiency, and the risk of on-target or off-target unwanted effects and chromosomal rearrangements. In this review, we highlight the latest progress in the development of in vivo liver-targeted genome editing approaches for the treatment of genetic disorders. We describe the technological advancements that are currently under investigation, the challenges to overcome for clinical applicability, and the future perspectives of this technology.

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Gene transfer and genome editing for familial hypercholesterolemia

Cited by 3 publications

References 150 publications

A narrative review of treatment modalities for familial hypercholesterolemia

A narrative review of treatment modalities for familial hypercholesterolemia

Advances in nucleic acid-targeted therapies for cardiovascular disease prevention

In vivo liver targeted genome editing as therapeutic approach: progresses and challenges

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