The First CRISPR Cures

Twelve years after Jennifer Doudna and Emmanuelle Charpentier published the paper that made CRISPR gene editing possible, the first generation of approved cures is reaching patients. Casgevy, the first CRISPR therapy approved for sickle cell disease, has now been used in more than five hundred patient initiations; personalised base-editing infusions for individual infants are beginning to work; the next generation of in-vivo CRISPR, base-editing and prime-editing therapies are in late-stage trials. The science is moving fast. The price tag — $2.2 million for a one-shot treatment — and the limited reach mean most of the world’s patients are not yet close to receiving the cure. This is the state of CRISPR medicine in October 2026: what has been cured, what is close, and what is still out of reach.

Casgevy: the first approved cure

Twelve years and a day after the 2012 Science paper that introduced CRISPR as a programmable gene-editing tool, the U.S. Food and Drug Administration approved the first therapy that uses it. On 8 December 2023, the agency cleared exagamglogene autotemcel — sold as Casgevy, developed by Vertex Pharmaceuticals and CRISPR Therapeutics — for sickle cell disease in patients 12 and older with recurrent vaso-occlusive crises.[1, 2] The approval came two months after the United Kingdom’s Medicines and Healthcare products Regulatory Agency had become the first regulator to say yes.[2]

Casgevy works by harvesting a patient’s own blood-forming stem cells, editing them ex vivo with CRISPR-Cas9 to disable a regulatory region of the BCL11A gene and reactivate fetal haemoglobin production, and then reinfusing them after myeloablative conditioning with busulfan. The result, in most treated patients, is the near-elimination of the sickling crises that drive sickle cell disease. In the pivotal CLIMB-121 trial, 92% of evaluable patients with at least 16 months of follow-up were free of vaso-occlusive crises for at least 12 months; 97% were free of hospitalisation for crisis for at least 12 months.[2, 14]

The real-world experience is now meaningful. Vertex reported in its 2025 annual results that 64 patients had been infused with Casgevy during 2025 — 30 of them in the fourth quarter alone — and that more than 500 patient initiations had occurred since launch.[2] On 1 July 2026, the FDA extended the indication to children aged 2 and older under the Commissioner’s National Priority Voucher programme.[1] The companion therapy lovotibeglogene autotemcel (Lyfgenia, bluebird bio / Genetix Bio) was approved the same day as Casgevy for sickle cell disease, using a different mechanism — a lentiviral vector that adds a functional copy of the beta-globin gene — and has been used in more than 100 patients.[10]

Both therapies are gruelling. The ex-vivo approach requires weeks of cell collection, myeloablative chemotherapy, and weeks of recovery. Both carry a U.S. boxed warning for haematologic malignancy. And both are priced for the U.S. market alone.

In-vivo CRISPR: editing inside the body

The next generation skips the cell-collection step entirely. In-vivo CRISPR therapies edit genes inside the patient’s body, delivered by lipid nanoparticles or viral vectors.

Intellia Therapeutics‘s lead candidate, NTLA-2001 (now nex-z), uses CRISPR-Cas9 packaged in lipid nanoparticles and delivered by intravenous infusion to switch off the TTR gene in the liver. In the Phase 1 trial published in the New England Journal of Medicine in 2024, a single 1.0 mg/kg dose produced a mean 89% reduction in serum transthyretin at 28 days, sustained at 12 months, with a corresponding improvement in clinical scores for the patients with hereditary transthyretin amyloidosis and cardiomyopathy.[3] The MAGNITUDE-2 Phase 3 trial in that indication is now enrolling. Intellia’s second candidate, NTLA-2002 for hereditary angioedema, has completed enrolment of the Phase 3 HAELO study.

Verve Therapeutics‘ VERVE-102 — acquired by Eli Lilly in 2025 — uses base editing to switch off the PCSK9 gene in the liver, with the aim of permanently lowering LDL cholesterol. In results published in the New England Journal of Medicine on 13 August 2026, a single infusion produced an 88% reduction in blood PCSK9 and a 62% reduction in LDL cholesterol at the top dose, durable at 18 months.[4] The same trial reported one treatment-related serious adverse event — a case of elevated liver enzymes that resolved.

The in-vivo approach is technically harder than ex vivo. The editing machinery has to reach the right tissue at the right dose, do its work, and clear. Off-target edits are easier to miss without the ability to characterise the cell product before infusion. The lipid nanoparticles that deliver the payload can trigger infusion reactions; the AAV vectors that some early designs used have their own immunogenicity issues. The first wave of clinical data suggests these problems are tractable, not solved.

Base editing and prime editing: beyond the original recipe

Two refinements of CRISPR chemistry have moved from the lab to the clinic in the past two years.

Beam Therapeutics‘ lead product, ristoglogene autogetemcel (risto-cel, formerly BEAM-101), is an ex-vivo base-editing therapy for sickle cell disease. The BEACON Phase 1/2 trial was published in the New England Journal of Medicine in 2026, and Beam expects to file a biologics licence application by year-end 2026.[5, 6] The same company’s BEAM-302, an in-vivo base-editing therapy for alpha-1 antitrypsin deficiency, began dosing in its global pivotal cohort in July 2026; 60 mg was selected as the optimal biological dose on the strength of data presented at the European Respiratory Society Congress in September 2026, showing mean AAT levels rising from 5.0 to 14.4 μM (above the 11 μM protective threshold) and a 93% proportion of corrected M-AAT at steady state.[5]

Prime Medicine‘s PM359 was the first prime-editing therapy administered in humans. The therapy is an autologous haematopoietic stem-cell product that uses prime editing to correct the most common disease-causing mutation in p47phox-deficient chronic granulomatous disease. In the initial two-patient report published in the New England Journal of Medicine in December 2025, both patients achieved durable restoration of NADPH oxidase activity — to 69% and 83% of neutrophils by day 30, far above the 20% threshold believed necessary for clinical benefit — with a safety profile consistent with busulfan conditioning alone.[7] The FDA granted PM359 Regenerative Medicine Advanced Therapy designation in June 2026.[8]

The chemistry of base editing and prime editing matters because it widens the range of edits possible. Standard CRISPR-Cas9 makes double-strand breaks and relies on the cell’s repair machinery to make a change; base editing makes a single-nucleotide change without a break; prime editing uses a reverse transcriptase to write new sequence directly into the target site. Each can fix mutations that standard CRISPR cannot, and each carries its own off-target profile.

The personalised fix

In February 2025, a baby named KJ Muldoon, then six months old, became the first patient to receive a personalised, on-demand gene-editing therapy — a base-editing infusion designed and manufactured for his specific mutation in the CPS1 gene. The team at the Children’s Hospital of Philadelphia and the University of Pennsylvania built the therapy in roughly six months.[9]

A one-year follow-up report in February 2026 said KJ was “thriving”: walking, talking, eating more protein than his metabolic condition had previously allowed, and free of the metabolic crises that would otherwise have been his likely outcome.[9] The same team has since launched a platform trial for seven urea-cycle disorders, with the first additional patients already dosed.

The personalised approach is the most ambitious extension of CRISPR medicine. It is also the most expensive: each bespoke therapy takes months and costs in the low millions of dollars. It is, for now, an exception, not a system.

Who gets left out

The medicines exist. The patients are mostly somewhere else.

Casgevy and Lyfgenia are priced at $2.2 million and $3.1 million per patient, respectively.[10] In the United States, the Centers for Medicare & Medicaid Services launched a Cell & Gene Therapy Access Model in January 2025 that ties Medicaid payments to outcomes, with 33 states, the District of Columbia and Puerto Rico participating as of mid-2026 — covering about 84% of U.S. Medicaid beneficiaries with sickle cell disease.[11]

In sub-Saharan Africa, where an estimated 80% of the world’s sickle cell patients live, the new therapies are effectively out of reach. The bone-marrow-conditioning regimen requires specialised centres; hydroxyurea, a $7-a-month standard-of-care drug, is itself inconsistently available.[10] Vertex has stated that it is working on access pathways, including potentially simpler regimens, but has not given a timeline.[10]

The in-vivo therapies, when they arrive, will be cheaper to manufacture and easier to deliver than the ex-vivo approach, and may be more practical in lower-resource settings. None of them has yet been approved for sickle cell disease. The first base-editing cure for an inherited disease, if it comes, will be priced for a different market than the ex-vivo therapies that came before it.

Where this leaves us

The first generation of CRISPR gene editing has reached patients. Casgevy is the proof that the 2012 science works in humans. The next generation — in-vivo base editing for cardiovascular disease, prime editing for immune disorders, personalised therapies for ultra-rare conditions — is moving through trials at a pace that would have looked implausible five years ago.

The second generation of challenges is harder. The price of a cure has to come down, or the cure has to reach patients who cannot pay. The off-target safety question has to be answered with longer follow-up. The 15-year post-treatment surveillance the FDA mandates for exa-cel has to actually happen. The conditioning regimen that makes ex-vivo therapy possible has to give way to something less toxic, or in-vivo approaches have to take over.

The science has come further, faster, than almost anyone expected. The medicine — the part that decides who actually gets cured — has come further than the headlines suggest, and not nearly as far as it will need to.

Therapy	Developer	Editing approach	Indication	Status (Oct 2026)	List price
Casgevy (exa-cel)	Vertex / CRISPR Therapeutics	Ex-vivo CRISPR-Cas9 (BCL11A enhancer)	Sickle cell disease; transfusion-dependent beta-thalassemia	FDA Dec 2023; EMA Feb 2024; pediatric expansion Jul 2026	$2.2M one-shot
Lyfgenia (lovo-cel)	bluebird bio / Genetix Bio	Ex-vivo lentiviral vector (βA-T87Q-globin)	Sickle cell disease	FDA Dec 2023	$3.1M one-shot
risto-cel (BEAM-101)	Beam Therapeutics	Ex-vivo base editing (HBG1/2 promoter)	Sickle cell disease	BEACON Phase 1/2 published in NEJM; BLA filing expected Q4 2026	TBD
BEAM-302	Beam Therapeutics	In-vivo base editing (PiZ correction)	Alpha-1 antitrypsin deficiency	Pivotal cohort dosing started Jul 2026; 60 mg dose selected	TBD
NTLA-2001 (nex-z)	Intellia Therapeutics	In-vivo CRISPR-Cas9 LNP (TTR KO)	Hereditary transthyretin amyloidosis	MAGNITUDE-2 Phase 3 enrolling	TBD
NTLA-2002	Intellia Therapeutics	In-vivo CRISPR-Cas9 LNP (KLKB1 KO)	Hereditary angioedema	HAELO Phase 3 enrolment complete	TBD
VERVE-102	Verve Therapeutics (Eli Lilly)	In-vivo base editing (PCSK9 KO)	Heterozygous familial hypercholesterolaemia; ASCVD	Phase 1/2 results published NEJM 13 Aug 2026	TBD
PM359	Prime Medicine	Ex-vivo prime editing (NCF1 delGT)	p47phox chronic granulomatous disease	First-in-human data published NEJM Dec 2025; RMAT Jun 2026	TBD
KJ Muldoon bespoke	CHOP / Penn	Personalised in-vivo base editing (CPS1)	CPS1 deficiency (single patient, then platform trial)	First dose Feb 2025; thriving at 1-yr follow-up; platform trial open	N/A (one-off)

References

1. U.S. Food and Drug Administration. “FDA Approves First Gene Therapy for Young Children with Sickle Cell Disease.” Press release, 1 July 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-young-children-sickle-cell-disease
2. Vertex Pharmaceuticals. Q4 2025 / 2025 annual report and investor disclosures. https://investors.vrtx.com/financials/sec-filings
3. Gillmore J.D., Gane E., Taubel J. et al. “CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis.” New England Journal of Medicine 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2309515
4. “In Vivo Base Editing of PCSK9 with VERVE-102.” New England Journal of Medicine 395(7):648 - 659, 13 August 2026. https://www.nejm.org/doi/full/10.1056/NEJMoa2501234
5. Beam Therapeutics. SEC Form 8-K and Q1 / Q2 2026 disclosures, plus ERS 2026 presentation. https://investors.beamtx.com/news-releases
6. “Ristoglogene Autogetemcel for Sickle Cell Disease” (BEACON trial). New England Journal of Medicine, 2026.
7. “Prime Editing for p47phox-Deficient Chronic Granulomatous Disease.” New England Journal of Medicine 394(12):1195 - 1203, 26 March 2026. https://pubmed.ncbi.nlm.nih.gov/41358590/
8. Prime Medicine. “Prime Medicine Receives U.S. FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for PM359.” Press release, 22 June 2026. https://www.biospace.com/press-releases/prime-medicine-receives-u-s-fda-regenerative-medicine-advanced-therapy-rmat-designation-for-pm359-for-the-treatment-of-chronic-granulomatous-disease-cgd
9. Musunuru K. et al. “Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease” (Baby KJ). New England Journal of Medicine 392(22):2235 - 43, 2025; one-year follow-up, CHOP / Penn press release, February 2026.
10. “New sickle cell gene therapies pose cost and access questions.” Axios, 9 December 2023. https://www.axios.com/2023/12/09/sickle-cell-gene-therapies-cost-access
11. “Expanding Access to Sickle Cell Gene Therapies for Patients with Medicaid.” Yale School of Medicine, 2025. https://medicine.yale.edu/news-article/expanding-access-to-sickle-cell-gene-therapies-for-patients-with-medicaid/
12. Carroll D. “The Clinical Landscape of CRISPR-Based Therapies.” Nature Reviews Drug Discovery, 2024 - 2025.
13. U.S. Food and Drug Administration. Cellular, Tissue and Gene Therapies Advisory Committee briefing documents, October 2023 (15-year follow-up rationale for exa-cel). https://www.fda.gov/advisory-committees/cellular-tissue-and-gene-therapies-advisory-committee
14. Frangoul H. et al. “Exagamglogene Autotemcel for Sickle Cell Disease” (CLIMB-121 trial). New England Journal of Medicine, 2024 - 2025. https://www.nejm.org/doi/full/10.1056/NEJMoa2309676