CRISPR Therapeutics
Details
A Boston-based biotechnology company developing in vivo CRISPR-Cas9 gene-editing therapeutics, with a pipeline concentrated on hepatically expressed targets delivered by lipid nanoparticle. Its cardiovascular portfolio is built on the principle that a single permanent edit to a liver-expressed gene can replace lifelong pharmacological therapy — targeting ANGPTL3 for atherogenic dyslipidemia, LPA for lipoprotein(a) elevation, and AGT for refractory hypertension.
Key Facts
Cardiovascular Pipeline
- CTX310 — ANGPTL3 (dyslipidemia): lipid-nanoparticle–encapsulated Cas9 mRNA plus guide RNA inducing a loss-of-function mutation in hepatocytes, given as a single intravenous infusion. Phase 1A first-in-human trial in 15 patients with refractory hypercholesterolemia, hypertriglyceridemia, or mixed dyslipidemia showed no dose-limiting toxic effects and no related serious adverse events, with −48.9% LDL cholesterol and −55.2% triglycerides at 0.8 mg/kg (sources/CRISPR-Cas9-NEJM-2025 — high)
- CTX320 — LPA (Lp(a) elevation): dose-dependent editing of LPA in primary human hepatocytes in vitro exceeding 80%; Lp(a) reduced by 94% in non-human primates at 7 months; a Phase 1 trial for Lp(a) elevation with established cardiovascular disease was being initiated (sources/gene-editing-acc-2026 — very high)
- CTX340 — AGT (refractory hypertension): LNP-based gene editing targeting hepatically expressed angiotensinogen, the master regulator of the renin–angiotensin–aldosterone system; advanced to clinical development. The first gene-editing therapy aimed at the RAAS rather than a lipid target (sources/gene-editing-acc-2026 — very high)
- Notable strategic feature: all three programs use LNP delivery to the liver and target genes whose loss-of-function variants are naturally tolerated — the same target-validation logic in each case (sources/gene-editing-acc-2026 — very high)
Trial Conduct and Sponsorship
- Funded the CTX310 Phase 1 trial and employs several of its authors, including co-authors from its Boston site (sources/CRISPR-Cas9-NEJM-2025 — high)
- Performed the initial statistical analysis of that trial; results were independently confirmed by statisticians at the Cleveland Clinic Coordinating Center for Clinical Research (sources/CRISPR-Cas9-NEJM-2025 — high)
- Data collection was outsourced to PPD, a contract research organisation (sources/CRISPR-Cas9-NEJM-2025 — high)
Competitive Landscape
- Verve Therapeutics is the principal competitor in hepatic cardiovascular gene editing, with VERVE-102 (PCSK9 base editing, Heart-2 Phase 1b) and VERVE-201 / Pulse-1 (ANGPTL3 base editing, Phase 1b, targeting homozygous familial hypercholesterolemia), plus VERVE-301 for LPA (sources/gene-editing-acc-2026 — very high)
- The two companies differ in modality: CRISPR Therapeutics uses CRISPR-Cas9 nuclease editing to install loss-of-function mutations, whereas Verve uses base editors, which avoid double-strand breaks (sources/gene-editing-acc-2026 — very high)
- CorrectSequence Therapeutics is separately running a base-editing trial targeting APOC3 in familial chylomicronemia syndrome (sources/gene-editing-acc-2026 — very high)
Contradictions / Open Questions
- Class-wide durability and safety are unproven. All cardiovascular gene-editing programs remain in Phase 1 with no outcomes data; whether permanent hepatic edits are durable over decades, and whether they carry late malignancy or hepatotoxicity risk, is unknown. FDA guidance recommends up to 15 years of follow-up (sources/gene-editing-acc-2026 — very high; sources/CRISPR-Cas9-NEJM-2025 — high)
- Hepatotoxicity signal across LNP-CRISPR programs. CTX310 produced one transient grade 2 transaminase elevation, and the MAGNITUDE Phase 3 trial of a different LNP-delivered CRISPR product was paused for severe hepatotoxicity including a death. Whether this is a delivery-platform class effect or target-specific is unresolved (sources/gene-editing-acc-2026 — very high)
- Pipeline breadth rests largely on preclinical data. Of the three cardiovascular programs, only CTX310 has reported clinical results in a peer-reviewed publication; CTX320 and CTX340 claims derive from non-human primate and in vitro work or conference reporting (sources/gene-editing-acc-2026 — very high)
- Commercial durability versus one-time dosing. A permanent single-dose cure is a scientific achievement but an unusual commercial model; how pricing and development incentives shape which programs advance is not addressed by the clinical literature (sources/gene-editing-acc-2026 — very high)
Connections
- Related to entities/CTX310 — lead cardiovascular asset
- Related to concepts/Lipid-Gene-Therapy — therapeutic area
- Related to concepts/ANGPTL3-Inhibition — CTX310 mechanism
- Related to concepts/Gene-Editing-Risk-Benefit-Framework — irreversibility and long-term follow-up requirements
- Related to concepts/CRISPR-Cas9-in-Channelopathies — shared editing platform in a different organ
- Related to entities/Familial-Hypercholesterolemia — target indication for ANGPTL3 and PCSK9 editing