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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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PCSK9 Base Editing Therapeutics and Ischemic Stroke

Josephin Wagner1, Andrew S Bell1, Falk W Lohoff1

  • 1Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland 20892-1540, United States.

ACS Chemical Neuroscience
|November 14, 2022
PubMed

Insights

Genetic gain-of-function variations in the PCSK9 gene increase cardiovascular disease risk. Novel genomic technologies like CRISPR and adenine base editing offer promising new therapeutic approaches for PCSK9-related conditions.

Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Molecular Biology

Background:

  • Gain-of-function variations in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene are linked to elevated cardiovascular disease (CVD) risk, including ischemic stroke.
  • Current PCSK9 inhibitors (PCSK9i) effectively reduce CVD and ischemic stroke risk, but novel therapeutic strategies are needed.

Purpose of the Study:

  • To discuss ongoing research in PCSK9 base editing.
  • To highlight future directions for PCSK9 base editing in cardiovascular disease and ischemic stroke prevention and treatment.

Main Methods:

  • Review of current research on PCSK9 base editing technologies.
  • Discussion of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 complex-mediated delivery and adenine base editing (ABE) for PCSK9 gene modification.

Main Results:

  • Ongoing work demonstrates the potential of base editing for PCSK9 modulation.
  • CRISPR-Cas9 and ABE present promising avenues for therapeutic intervention.

Conclusions:

  • PCSK9 base editing represents a novel and promising frontier in managing cardiovascular disease and ischemic stroke.
  • Further research into PCSK9 base editing is crucial for developing advanced preventative and therapeutic strategies.

Keywords:
Proprotein convertase subtilisin-kexin type 9 (PCSK9)adenine base editorscardiovascular disease (CVD)cholesterolclustered regularly interspaced short palindromic repeats (CRISPR)gene editinggeneticsischemic strokelow-density lipoprotein-cholesterol (LDL-C)

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