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CRISPR therapies (Casgevy + base/prime editing)

Casgevy approval (December 2023) marked first FDA-approved CRISPR therapy; 23+ clinical trials now active with base/prime editing showing efficacy in rare genetic diseases and potential for broader indications.

What to watch next

Intellia's FDA approval filing 2026, Beam and Prime Medicine accelerated approvals late 2026-2027, expanded in vivo CRISPR programs, and next-generation base/prime editors with improved efficiency and safety profiles.

Key sub-ideas & techniques

• Ex vivo CRISPR/Cas9 (Casgevy) — CRISPR Therapeutics + Vertex's Casgevy was the first FDA-approved CRISPR therapy (Dec 2023) — ex vivo edit of HSCs to reactivate fetal hemoglobin in sickle-cell disease and beta-thalassemia. [source]
• Base editing — David Liu's base editors (cytosine and adenine) make single-letter DNA changes without double-strand breaks — Beam (BEAM-101 for sickle cell, BEAM-302 for AATD) and Verve (PCSK9 for cardiovascular) are the lead programs. [source]
• Prime editing — Liu lab's prime editing, the 'search-and-replace' of genome editing, achieved its first-ever human evidence in 2025 with PM359 in chronic granulomatous disease, on an FDA accelerated-approval path. [source]
• In vivo CRISPR via LNP — Intellia's NTLA-2002 (lonvoguran ziclumeran) for hereditary angioedema cut attacks ~87% in Phase 3 — the first Phase-3-positive in-body CRISPR therapy and a template for the rest of the genome. [source]
• Epigenome editing — dCas9 fused to silencing or activating domains can switch genes off or on without cutting DNA — Tune Therapeutics, Chroma Medicine, and Epic Bio are running the first programs (Tune's TUNE-401 for HBV in trials). [source]
• In vivo prime editing reaches the clinic — Prime Medicine's PM577a, an LNP-formulated prime editor delivered IV to hepatocytes, is the first in vivo prime editing therapy authorized for human trials, correcting the ATP7B H1069Q mutation in Wilson Disease. [source]
• Caribou CB-011 allogeneic CRISPR CAR-T — CRISPR-edited allogeneic anti-BCMA CAR-T immune-cloaked via B2M-knockout/HLA-E-fusion; 92% ORR, 83% CR/sCR, 91% MRD-negativity in a 12-patient r/r multiple myeloma cohort, 50% still in CR at 15 months (CaMMouflage phase 1, EHA 2026). [source]
• AstraZeneca/Neogene NT-175 CRISPR TCR-T (solid tumors) — CRISPR-edited (TCR + TGFβR2 knockout) autologous T-cell therapy targeting the shared TP53 R175H neoantigen; acceptable safety and early anti-tumor efficacy signals in a phase 1 across pancreatic, colorectal and breast tumors (ASCO 2026, Abstract 2506). [source]
• HuidaGene HG302 DMD trial fatality disclosure — Delayed disclosure of a 2025 death in an investigator-led CRISPR/DMD trial (AAV-triggered ARDS/cytokine), intensifying transparency/oversight scrutiny of China's investigator-initiated gene-editing studies. [source]
• Intellia nex-z HLA pharmacogenomic signal — HLA-allele carriers showed the highest liver enzyme elevations from in vivo CRISPR ATTR therapy nex-z; a pharmacogenomic safety signal shared with FDA as Phase 3 resumes. [source]
• Post-Cas9 proprietary editing platforms — In-house editor architectures distinct from CRISPR/Cas9 reaching first-in-human trials. [source]
• CD19 CAR-T reverses refractory rheumatoid arthritis in Nature Medicine — Charite Berlin's phase 1 COMPARE trial treated 6 RA patients refractory to up to 8 prior therapies; all six showed markedly reduced disease activity and three were in sustained drug-free remission at up to one year. [source]
• BEAM-302 base editing durably raises AAT above threshold in 29 patients — At ERS Congress 2026, Beam Therapeutics reported a single dose of BEAM-302 (in vivo adenine base editor correcting the SERPINA1 mutation) durably raised functional alpha-1 antitrypsin above the protective threshold across 29 dosed patients; mild-to-moderate infusion reactions in 41%. Backfill: ERS late-breaker (Sep 5-9, press release Sep 8) that drew continued analyst and specialist-press pickup through the Sep 11-18 window; first time logged here. [source]
• FDA clears trial of dual CD20/BCMA CAR-T C-CAR168 for progressive MS — The FDA authorized Abelzeta Pharma's Phase 1b/2 trial of C-CAR168, an autologous CAR-T targeting both CD20 and BCMA, in treatment-refractory secondary/primary progressive MS; prior data in 2 SPMS patients showed reduced MRI lesion burden and improved disability scores. [source]
• In vivo lentiviral CD19 CAR-T shows early benefit in 16 neuro-autoimmune patients — NEJM report on JY231, an off-the-shelf lentiviral vector generating CD19 CAR-T cells directly in vivo (no manufacturing or lymphodepleting chemo), found complete B-cell depletion and preliminary disability improvement across 16 refractory neurologic autoimmune patients. [source]
• PM647 — In vivo, LNP-delivered prime editor correcting the SERPINA1 PiZ mutation to restore functional alpha-1 antitrypsin protein, addressing both lung and liver manifestations of AATD. [source]

Current frontier

• Casgevy (exagamglogene autotemcel) FDA-approved December 8, 2023, for sickle cell disease in patients ≥12 years; uses CRISPR/Cas9 to induce fetal hemoglobin, eliminating vaso-occlusive crises in clinical trials. [source]
• Intellia's lonvoguran ziclumeran (in vivo CRISPR therapy) reduced hereditary angioedema attacks by 87% vs. placebo in Phase 3 HAELO trial (announced April 27, 2026); rolling FDA BLA submission initiated. [source]
• Beam Therapeutics' BEAM-302 (base editing for alpha-1 antitrypsin deficiency) dosed 29 patients with well-tolerated safety profile and no dose-limiting toxicities; FDA RMAT designation granted; optimal 60 mg dose selected for pivotal development. [source]
• Prime Medicine's PM359 (prime editing ex vivo therapy for chronic granulomatous disease) shows first human safety/efficacy data with FDA 'plausible mechanism' pathway grant; company pursuing accelerated approval with potential 2026 alignment meeting. [source]
• As of 2026, 23+ clinical trials are active using base editing or prime editing for leukemias, hypercholesterolemia, AATD, sickle cell disease, beta-thalassemia, and chronic granulomatous disease. [source]
• Intellia's lonvo-z became the first in vivo CRISPR therapy to win a positive pivotal Phase 3 (HAELO), cutting hereditary angioedema attacks 87% vs placebo (p<0.0001) with 62% attack-free over 6 months; NEJM-published, rolling BLA underway for 1H 2027 launch. [source]
• Autolus' fast-off-rate CD19 CAR-T obe-cel showed 83% (5/6) remission (per standard lupus criteria) at target dose, with several complete/partial renal responses, in severe refractory lupus in the Phase 1 CARLYSLE trial, presented at EULAR 2026. [source]
• Beam BEAM-304 (in vivo LNP adenine base editor for PKU/PAH) cleared FDA IND June 18 2026; preclinical normalization of plasma Phe. [source]
• Dual CD19/BCMA CAR-T (Beijing GoBroad Boren) induced sustained remission in 11 refractory systemic-sclerosis patients (EULAR 2026). [source]
• VERVE-102 (Verve/Lilly) in vivo base editing cut PCSK9 ~88% and LDL-C ~62% (n=35, Heart-2), durable >1yr, no dose-limiting toxicities (NEJM). [source]
• bioRxiv preprint: in vivo epigenome editing gave the most durable PCSK9 silencing vs nuclease/deaminase editing and siRNA (mRNA editors in Arcturus LUNAR LNPs, mice). [source]
• At EAACI 2026 (presented Jun 13, 2026) and published in NEJM, Intellia's lonvoguran ziclumeran (lonvo-z), a single-dose LNP-delivered CRISPR therapy inactivating KLKB1 in the liver, cut mean monthly hereditary-angioedema attacks by 87% vs placebo with 62% of patients attack-free over 6 months — the first positive pivotal Phase 3 for an in vivo CRISPR therapy; rolling BLA targeting 1H 2027. [source]
• Two Nature papers show the nuclease Cas12a2 can be programmed to detect disease-linked RNA (e.g., mutant KRAS/TP53) and trigger DNA-shredding cell death, eliminating tumor cells in mouse models while sparing healthy cells; spotlighted in Nature's July 14, 2026 News & Views. [source]
• CASTLE basket trial (EULAR 2026): CD19 CAR-T zorpocabtagene autoleucel — 9/10 SLE patients in DORIS remission at 6 mo, drug-free through 24 wk; 1/28 SLE relapse at median 13 mo. [source]
• EHA 2026: CARsgen allogeneic CAR-T CT0596 (BCMA, 8 pts) and CT1190B (CD19/CD20, 13 lymphoma pts); Phase Ib planned 2026. [source]
• A Cas9-nickase editor fusing engineered adenine/cytosine deaminases with alkyladenine DNA glycosylases achieved simultaneous triple-base editing at 5.7-41% efficiency at endogenous human sites, with up to 3.2x more allelic diversity than dual A-C editors. [source]
• FDA accepted Intellia's lonvo-z (HAE) BLA with Priority Review; PDUFA March 10, 2027; Phase 3 HAELO: 87% attack reduction vs placebo. [source]
• BEAM-302 (in vivo base editing, AATD): 18-mo durability, total AAT >11 µM at 60mg, Z-AAT -84%, M-AAT 93% of circulating protein; pivotal cohort dosing (ERS 2026). [source]
• Novartis halted eight rap-cel autoimmune CAR-T trials after 3 fatal IEC-HS cases; BMS paused zola-cel enrollment (reported Aug 31-Sep 1, 2026). [source]
• At MSToronto2026 (Oct 21-23), Imviva's allogeneic CD19/BCMA CAR-T CTA313 showed early signs of disability stabilization and manageable safety in the first 3 refractory progressive MS patients of an open-label Phase 1. Very small, preliminary; no efficacy conclusions. [source]

Key people

• Feng Zhang James and Patricia Poitras Professor of Neuroscience; Core Member Broad Institute · MIT McGovern Institute; Broad Institute of MIT and Harvard [source]
• David Liu Richard Merkin Professor; Director Merkin Institute; HHMI Investigator · Harvard University; Broad Institute of MIT and Harvard [source]
• Editas Medicine/CRISPR Therapeutics Leadership CEO (Casgevy development) · CRISPR Therapeutics; Vertex Pharmaceuticals (co-developer) [source]
• John Leonard Chief Executive Officer · Intellia Therapeutics [source]
• Keith Gottesdiener Chief Executive Officer · Prime Medicine [source]

Startups & labs to watch

• Prime Medicine (prime editing platform) Prime Medicine Inc. · STARTUP · Series B: $200M+ (2022); backed by Jeff Bezos and others — First-ever prime editing human data (PM359 for CGD); pursuing accelerated approval pathway 2026; expects clinical data may support approval with FDA alignment meeting ongoing. [source]
• Verve Therapeutics (base editing for cardiovascular disease) Verve Therapeutics Inc. · STARTUP · Public company; venture-backed with multiple funding rounds — VERVE-102 Phase 1b data showed ~50% LDL reduction in highest-dose patients; shifted to improved LNP formulation after VERVE-101 liver enzyme abnormalities; targeting PCSK9 base editing. [source]
• Intellia Therapeutics (in vivo CRISPR for rare diseases) Intellia Therapeutics Inc. · STARTUP · Public company; multiple funding rounds and partnerships — First Phase 3 in vivo CRISPR data (hereditary angioedema); rolling FDA submission 2026; expects U.S. launch H1 2027 if approved; expanding to other rare genetic diseases. [source]
• Beam Therapeutics (base editing for genetic disease) Beam Therapeutics Inc. · STARTUP · Public company; founded by Liu, Barrangou, and others with $300M+ raised — BEAM-302 advancing to pivotal development for AATD with 60 mg optimal dose; BEAM-301 (GSD-Ia) data expected 2026; RMAT designation supporting accelerated pathway. [source]
• EDIT-401 (LDLR upregulation, in vivo gene editing) Editas Medicine · STARTUP · Public (NASDAQ: EDIT) — Lead in vivo program targeting hyperlipidemia/HeFH; >=90% LDL-C lowering in NHPs; FIH expected 2026 with human PoC by year-end; positions Editas as direct competitor to Verve/Lilly in cardiovascular gene editing. [source]
• Autolus Therapeutics Autolus Therapeutics plc · STARTUP · Public (Nasdaq: AUTL) — Commercial-stage CAR-T company (obe-cel/Aucatzyl approved in B-ALL) extending its fast-off-rate CD19 platform into autoimmune disease (lupus), a fast-emerging high-value indication for cell therapy. [source]
• Caribou Biosciences Caribou Biosciences (allogeneic CRISPR CAR-T) · COMPANY — Entity reconciliation: developer of CB-011 (off-the-shelf, immune-cloaked anti-BCMA CAR-T); a lead player in the allogeneic/in-vivo cell-engineering gap theme. [source]
• Charite - Universitatsmedizin Berlin Charite - Universitatsmedizin Berlin · LAB · n/a — Leading academic driver of CAR-T-for-autoimmune-disease trials, generalizing from lupus to rheumatoid arthritis [source]
• Abelzeta Pharma Abelzeta Pharma · STARTUP — Pushing dual-antigen CAR-T into neuro-autoimmune indications, one of the fastest-moving frontiers in cell therapy [source]
• SNIPR Biome SNIPR Biome · BIOTECH · CARB-X supported — Extends CRISPR gene-editing tools beyond human genome correction into precision antimicrobial phage therapy, a distinct application vector for editing platforms; CARB-X backed. [source]
• Epicrispr Biotechnologies Epicrispr Biotechnologies · BUSINESS — First clinical evidence for an AAV-delivered epigenetic silencer (DUX4); could validate editing without DNA cuts. [source]
• Kyverna Therapeutics Kyverna Therapeutics · BUSINESS — Likely first FDA-approved CAR-T for autoimmune disease. [source]
• Imviva Biotech Imviva Biotech · STARTUP — Off-the-shelf dual-target CAR-T entering autoimmune trials while autologous rivals (Novartis, BMS) are paused on safety [source]