Did One Tiny Tweak Just Solve Heart Disease?

Brad Stanfield

Jun 8, 2026

Episode description

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Here are the links to the research papers referenced in the video:
Verve-102 adverse events
https://www.cgtlive.com/view/verve-moves-on-second-gen-cardiovascular-crispr-therapy-verve-102-adverse-events

Framingham Heart Study — about
https://www.framinghamheartstudy.org/fhs-about/

Optimal LDL 50–70 mg/dL
https://pubmed.ncbi.nlm.nih.gov/15172426/

LDL causes ASCVD (EAS consensus)
https://academic.oup.com/eurheartj/article/38/32/2459/3745109

Broken PCSK9 protects against CHD
https://www.nejm.org/doi/full/10.1056/NEJMoa054013

Lower LDL extends lifespan (MR)
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.14811

CRISPR-Cas9 discovery history
https://pmc.ncbi.nlm.nih.gov/articles/PMC9377665/

CRISPR acquired resistance (2007)
https://embryo.asu.edu/pages/crispr-acquired-resistance-against-viruses-2007

CRISPR is bacterial immunity
https://www.science.org/doi/10.1126/science.1138140

Programmable Cas9 DNA cleavage
https://www.science.org/doi/10.1126/science.1225829

2020 Nobel Chemistry for CRISPR
https://pmc.ncbi.nlm.nih.gov/articles/PMC7782372/

CRISPR causes large deletions
https://pmc.ncbi.nlm.nih.gov/articles/PMC6390938/

SCID-X1 gene therapy leukemia
https://www.jci.org/articles/view/35700

David Liu — Broad bio
https://www.broadinstitute.org/bios/david-liu

David Liu profile — Harvard Magazine
https://www.harvardmagazine.com/science/david-liu-harvard-gene-editing-research-disease-cures

VERVE-102 Heart-2 trial (NEJM)
https://www.nejm.org/doi/full/10.1056/NEJMoa2601283

Intellia MAGNITUDE clinical hold
https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-provides-update-magnitude-clinical-trials

Intellia nex-z patient death
https://www.cgtlive.com/view/patient-treated-trial-intellia-transthyretin-amyloidosis-gene-editing-therapy-nex-z-dies

Liu Breakthrough Prize / Tapley — Harvard Gazette
https://news.harvard.edu/gazette/story/2025/04/rewriting-genetic-destiny-gene-base-editing/

Base-edited CAR7 T-cells in T-ALL (NEJM)
https://www.nejm.org/doi/full/10.1056/NEJMoa2505478

PCSK9 base editing in primates (Nature)
https://www.nature.com/articles/s41586-021-03534-y

Lilly VERVE-102 results
https://investor.lilly.com/news-releases/news-release-details/single-dose-lillys-pcsk9-base-editor-verve-102-reduced-pcsk9-88

Thumbnail by James Kelly
Video edited by Troy Young
Script by John Milliken

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Mindsip insights from this episode:

Leverage broken PCSK9 gene to reduce coronary heart disease risk

People with a naturally broken PCSK9 gene have an 89% lower lifetime risk of coronary heart disease, even with other risk factors like smoking or diabetes.

#genetics

#heart

Silence PCSK9 gene with Verve 102 therapy infusion

The Verve 102 therapy uses a base editor that arrives as messenger RNA, makes one single letter change to silence the PCSK9 gene, and then disappears within days.

#genetics

#therapy

Target PCSK9 gene to manage LDL cholesterol and reduce heart disease risk

LDL cholesterol is the pivotal risk factor for heart disease, and a single overactive gene called PCSK9 is a primary cause of high LDL.

#cholesterol

#genetics

Lower LDL cholesterol by 62% with Verve 102 infusion

A single infusion of Verve 102 lowered LDL cholesterol by 62% in high-risk patients already on statins, with the effect lasting up to 18 months so far.

#clinical-trial

#LDL

Leverage PCSK9 gene for heart health and longevity

In addition to reducing heart disease, having a naturally faulty PCSK9 gene has also been associated with a longer lifespan.

#genetics

#longevity

Fix delivery vehicle to enhance gene editing success

The initial trial failure was caused by the delivery vehicle (the lipid nanoparticle), not the gene editor, and was fixed by swapping a lipid and adding a sugar tag.

#genetics

Utilize base editing for safer gene modification

A new technique called 'base editing' avoids the risks of traditional CRISPR by chemically swapping a single DNA letter instead of cutting both DNA strands.