Curing inherited diseases with a single gene-editing treatment

How far are we from curing inherited diseases with a single gene-editing treatment?

Gene-editing treatments for inherited disease are approved, but only in one form so far. Casgevy edits a person's blood stem cells outside the body. It was approved in the US for sickle cell disease in December 2023, and 64 people had cells reinfused in 2025, according to Vertex as reported by BioPharma Dive. Treatments that edit cells inside the body are at an earlier stage. A phase 3 trial of an in vivo CRISPR treatment for hereditary angioedema reported an 87% fall in attacks, and one infant received a treatment designed for his own mutation in 2025. None of the in vivo treatments reviewed has been approved.

AI illustration · Illustrative scene, not a photograph of the specific device or experiment.
WHERE WE AREPilots

Close. Early pilots are running in the real world.

Ex vivo gene editing is approved and in use for two blood disorders, but in small numbers. In vivo editing, which would reach more diseases, has one positive phase 3 result for a single disease, with a rolling regulatory submission under way, and one patient-specific case. None of the in vivo treatments reviewed has been approved. That places the overall goal at pilot: the approach works for selected patients, but it is not yet a routine treatment for inherited disease.

The tech tree

Everything recorded on Vrulum that this future needs, oldest foundations at the top and the goal at the bottom. Lines show what each step requires.

What it takes: Curing inherited diseases with a single gene-editing treatment Unlocked Being researched Locked
  1. 2016Base and prime gene editingResearch and prototypes Being researched.
  2. 2025In vivo gene editingResearch and prototypes Being researched.
  1. 2023Ex vivo edited blood stem cells approved for sickle cell diseaseDone Unlocked.
  2. 2025Ex vivo treatment used in routine careDone Unlocked.
  3. 2025Patient-specific in vivo base editing for one infantDone Unlocked.
  4. 2026Phase 3 in vivo editing for ATTR amyloidosis (nex-z)In progress Being researched.
  5. 2026Regulatory filing for in vivo treatment of hereditary angioedemaIn progress Being researched.
  6. 2026Phase 3 HAELO trial of in vivo CRISPR for hereditary angioedemaDone Unlocked.
  7. 2027Approval and US launch of an in vivo gene-editing treatmentNot started Locked.
  8. Date not recordedIn vivo editing in tissues other than the liverNot started Locked.
  9. Date not recordedRoutine one-time editing treatments for several inherited diseasesNot started Locked.
  1. GoalCuring inherited diseases with a single gene-editing treatmentGoalRequires: In vivo gene editing, Base and prime gene editing, Ex vivo edited blood stem cells approved for sickle cell disease, Ex vivo treatment used in routine care, Patient-specific in vivo base editing for one infant, Phase 3 HAELO trial of in vivo CRISPR for hereditary angioedema, Regulatory filing for in vivo treatment of hereditary angioedema, Approval and US launch of an in vivo gene-editing treatment, Phase 3 in vivo editing for ATTR amyloidosis (nex-z), In vivo editing in tissues other than the liver, Routine one-time editing treatments for several inherited diseases. Locked.

The road so far

4 of 9 steps done, 2 in progress.

  1. Done · 8 Dec 2023Ex vivo edited blood stem cells approved for sickle cell disease

    The FDA approved Casgevy on 8 December 2023 for people aged 12 and over with sickle cell disease and recurrent vaso-occlusive crises. In the single-arm trial, 44 patients were treated and 31 had enough follow-up to be evaluated. Of those 31, 29 (93.5%) were free of severe crises for at least 12 consecutive months within a 24-month follow-up. The trial had no comparison group. [1][2]

  2. Done · 2025Ex vivo treatment used in routine care

    Vertex reported that 64 patients had cells reinfused with Casgevy in 2025, and that Casgevy revenue for 2025 was $116 million, as reported by BioPharma Dive. BioPharma Dive reports that Vertex estimates about 16,000 people in the US are eligible for Casgevy, and that many of them are covered by Medicaid. The sources do not give a cumulative count of treated patients since approval. [3][2]

  3. Done · Feb 2025Patient-specific in vivo base editing for one infant

    An infant with severe CPS1 deficiency received a base-editing treatment designed for his own mutation. The first infusion was given in late February 2025, when he was between six and seven months old, and further doses followed in March and April. By April 2025 he had received three doses. He tolerated more dietary protein and needed less nitrogen-scavenger medicine. The researchers report no serious side effects as of April 2025 and say longer follow-up is needed. [4]

  4. Done · 13 Jun 2026Phase 3 HAELO trial of in vivo CRISPR for hereditary angioedema

    The HAELO trial enrolled 80 people, 52 to lonvoguran ziclumeran (lonvo-z) and 28 to placebo. Lonvo-z was given as a single dose. The release reports an 87% reduction (p<0.0001) in mean monthly attacks compared with placebo. The share of people who were entirely attack-free and therapy-free over the six-month efficacy period was 62% with lonvo-z and 11% with placebo. The release reports no serious adverse events in the lonvo-z arm, and says all reported treatment-emergent adverse events were mild or moderate. The data cutoff was 10 February 2026, and the release does not state follow-up beyond week 28. [5]

  5. In progress · Apr 2026Regulatory filing for in vivo treatment of hereditary angioedema

    Intellia's June 2026 release says a rolling Biologics License Application for lonvo-z was initiated in April. The release does not say whether the submission is complete. [5]

  6. Not started · 2027Approval and US launch of an in vivo gene-editing treatment

    Intellia expects regulatory approval and a US launch of lonvo-z in the first half of 2027. The outcome of the review is not known. [5]

  7. In progress · 27 Jan 2026Phase 3 in vivo editing for ATTR amyloidosis (nex-z)

    The nex-z programme (nexiguran ziclumeran, also known as NTLA-2001) has phase 3 trials for transthyretin amyloidosis. In October 2025 a patient in the MAGNITUDE trial had grade 4 liver transaminase elevations and raised bilirubin, and the FDA placed clinical holds on both trials. In its 6 November 2025 release, Intellia said the patient had died, and the treating physician reported complicating comorbidities. In January 2026 the FDA lifted the hold on MAGNITUDE-2, with enhanced liver monitoring and a target of about 60 patients. The hold on MAGNITUDE was still in place in that release. [6][7]

  8. Not startedIn vivo editing in tissues other than the liver

    The in vivo programmes reviewed for this record are aimed at the liver. Nex-z is designed to inactivate the TTR gene in the liver. Reaching muscle, brain, lung or blood-forming stem cells would need other delivery methods, and none is shown in these sources. [6]

  9. Not startedRoutine one-time editing treatments for several inherited diseases

    A treatment that works for many inherited diseases, with a repeatable manufacturing and regulatory route, has not been shown. The sources reviewed describe a different editing target for each in vivo treatment: lonvo-z targets the KLKB1 gene and nex-z targets TTR. [5][6]

Why it matters

A single treatment that corrects the cause of an inherited disease could replace some repeated care, such as regular infusions or long-term medicines. Each disease needs its own editing design, delivery method and long-term safety record, so progress comes disease by disease. The cost is also a barrier: the US list price of Casgevy is $2.2 million, which raises questions about who can receive these treatments.

What stands in the way

  • Durability and long-term safety are not established. The HAELO primary observation period covered infusion through week 28 after a single dose, and the release does not state longer follow-up. The KJ treatment was reported with follow-up measured in months.
  • Liver safety is a live concern for in vivo editing. A patient in the nex-z MAGNITUDE trial had grade 4 liver transaminase elevations and raised bilirubin after dosing, and the FDA placed holds on both nex-z phase 3 trials.
  • Delivery beyond the liver is not shown. The sources reviewed describe liver-directed programmes, and reaching muscle, brain, lung or blood-forming stem cells would need other methods.
  • Bespoke treatments do not scale yet. The infant's editor was designed for his own mutation, so it treats only that mutation.
  • Price and access are unresolved. The US list price of Casgevy is $2.2 million, and Medicaid's budget and price-reporting rules limit outcomes-based deals, according to the December 2023 BioPharma Dive report.

Published forecasts

What others have predicted. These are their estimates, not ours.

WhoForecastTimeframeMade
Intellia Therapeutics (company statement)Intellia expects regulatory approval and a US launch of lonvo-z for hereditary angioedema in the first half of 2027. This is a company expectation, not an independent forecast. [5]202713 Jun 2026

Signals to watch

  • The FDA decision on the lonvo-z Biologics License Application, which Intellia expects in the first half of 2027.
  • Longer follow-up from the HAELO trial, including any events after week 28.
  • Liver monitoring results from MAGNITUDE-2, and any change to the MAGNITUDE hold.
  • A second patient-specific in vivo editing treatment reported with a defined follow-up period.
  • Human data from in vivo editing outside the liver.
  • Casgevy patient numbers and pricing, as Vertex reports them each quarter.

Sources

  1. government report
    FDA approves first gene therapies to treat patients with sickle cell disease
    US Food and Drug Administration, 8 Dec 2023.
  2. news
    BioPharma Dive report on the list prices of sickle cell gene therapies (Casgevy and Lyfgenia)
    BioPharma Dive, 8 Dec 2023.
  3. news
    BioPharma Dive report on Vertex Q4 2025 earnings, including Casgevy revenue and patient numbers
    BioPharma Dive, 13 Feb 2026.
  4. university press release
    World's first patient treated with personalized CRISPR gene editing therapy
    Children's Hospital of Philadelphia, 15 May 2025.
  5. company announcement
    Intellia Therapeutics reports additional positive phase 3 results for lonvoguran ziclumeran (lonvo-z) in patients with hereditary angioedema
    Intellia Therapeutics (via GlobeNewswire and BioSpace), 13 Jun 2026.
  6. company announcement
    Intellia Therapeutics Q3 2025 financial results and recent updates (Exhibit 99.1)
    Intellia Therapeutics, via US Securities and Exchange Commission, 6 Nov 2025.
  7. company announcement
    Intellia Therapeutics announces FDA lift of clinical hold on MAGNITUDE-2 Phase 3 clinical trial in ATTRv-PN
    Intellia Therapeutics (via GlobeNewswire and BioSpace), 27 Jan 2026.

Last reviewed 21 Oct 2026.