Skip to content
ContentLora

    Tip: press / anywhere to search.

    technology

    CRISPR-Cas9

    Also known as CRISPR, Cas9, SpCas9, CRISPR/Cas9

    CRISPR-Cas9 is a DNA-cutting enzyme system from bacterial immunity that a guide RNA can program to cut a chosen DNA site.[1][2] It is the basis of Casgevy, the first approved CRISPR medicine, and of in vivo therapies now in late-stage trials or FDA review.[3][4]

    Editor reviewedStrict sourcingUpdated Gene editing and gene therapyLife sciencesHealth and medicine
    Key facts

    CRISPR-Cas9 is a programmable genome-editing tool. NHGRI describes it as simpler, faster, cheaper and more accurate than older genome-editing methods.[5]

    Origins

    The system comes from bacterial adaptive immunity.[1] In 2012, Jinek, Doudna, Charpentier and colleagues showed that a two-RNA structure directs the Cas9 protein to make double-stranded breaks in a matching DNA target. They pointed to its potential for RNA-programmable genome editing.[2] Doudna and Charpentier shared the 2020 Nobel Prize in Chemistry for the work.[6]

    How it is used in medicine

    The Cas9 therapies below use the cut to switch off a gene or a gene control region.

    • Ex vivo. Casgevy edits a patient’s blood stem cells outside the body at an enhancer of BCL11A, a gene that represses fetal hemoglobin. The edited cells make more fetal hemoglobin.[7] The FDA approved it in December 2023 as the first therapy using CRISPR/Cas9.[3]
    • In vivo. Lipid nanoparticles carry Cas9 mRNA and a guide RNA to the liver. NTLA-2001 lowered blood TTR protein by a mean 87% at its higher dose in a 2021 study.[8] Lonvo-z inactivates KLKB1 to treat hereditary angioedema, and its application is under FDA Priority Review.[9][4] CTX310 edits ANGPTL3 to lower blood lipids.[10]

    In vivo results in detail

    The most complete in vivo CRISPR data come from Intellia’s lonvo-z. In the Phase 3 HAELO trial, 80 patients with hereditary angioedema were randomized 2:1 to a single 50 mg infusion or placebo.[11] Lonvo-z cut attacks by 87% compared with placebo over weeks 5 to 28, and 62% of treated patients were free of attacks and of other preventive therapy.[12] No serious or Grade 3 or higher adverse events were reported in the lonvo-z group at a median 7.5 months of follow-up.[11]

    CRISPR Therapeutics reported one-year follow-up for CTX310 in August 2026. At the highest dose, mean ANGPTL3 was 79% below baseline, triglycerides 48% and LDL cholesterol 53% (company-reported, also published in NEJM).[13] In the published Phase 1 trial, two of 15 participants had serious adverse events, and the authors reported no dose-limiting toxic effects related to CTX310.[14]

    Intellia’s nex-z trials were paused after a patient had a severe liver reaction in 2025, and resumed in 2026 with enhanced liver monitoring.[15][16] An analysis of more than 600 trial samples later linked the largest liver enzyme rises to one HLA gene variant.[17] The intellia-therapeutics and crispr-therapeutics pages have details.

    Limits and successors

    Two newer tool families avoid cutting both DNA strands: base-editing, which converts one base into another without cutting both strands,[18] and prime-editing, which writes small edits from an RNA template.[19] Off-target editing remains a regulatory concern: Casgevy’s prescribing information includes a warning about it.[20] Getting Cas9 into tissues other than blood stem cells and the liver is still hard.[21] The FDA has published draft guidance on using next-generation sequencing to look for unintended edits.[22]

    Status in October 2026

    Casgevy is approved in 39 countries as of August 2026.[23] In the US it is approved from age 2.[24] No in vivo CRISPR therapy has yet been approved. Intellia says lonvo-z would be the first if the FDA approves it, and the agency’s target date is 10 March 2027.[4]

    Questions readers ask

    Who developed CRISPR-Cas9 genome editing?

    A 2012 Science paper by Jinek, Doudna, Charpentier and colleagues showed that Cas9 could be programmed by RNA to cut DNA. Doudna and Charpentier shared the 2020 Nobel Prize in Chemistry for it.[2][6]

    What is the first approved CRISPR-Cas9 medicine?

    Casgevy, for sickle cell disease and transfusion-dependent beta-thalassemia, approved in the UK in November 2023 and the US in December 2023.[25][3]

    What are the main risks of Cas9 editing?

    Unintended edits at other sites are one concern, and Casgevy's label warns of off-target genome editing risk. Long-lasting Cas9 expression from viral vectors may raise that risk.[20][26]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      CRISPR-Cas9 comes from an adaptive immune system that bacteria use, which researchers repurposed as a programmable DNA-cutting tool. confirmedas of 2026-10-10

    2. [2]

      A 2012 Science paper by Jinek, Doudna, Charpentier and colleagues showed that a two-RNA structure directs the Cas9 protein to make double-stranded breaks in target DNA, and highlighted its potential for RNA-programmable genome editing. confirmedas of 2026-10-10

    3. [3]

      On 8 December 2023 the FDA approved Casgevy, the first FDA-approved therapy using CRISPR/Cas9, for people aged 12 and older with sickle cell disease and recurrent vaso-occlusive crises. confirmedas of 2026-10-10

    4. [4]

      On 8 September 2026 Intellia said the FDA had accepted its lonvo-z application with Priority Review and a target action date of 10 March 2027; the company says lonvo-z would be the world's first in vivo CRISPR-based therapy if approved. confirmedas of 2026-10-10

    5. [5]

      The US National Human Genome Research Institute describes CRISPR as simpler, faster, cheaper and more accurate than older genome-editing methods. confirmedas of 2026-10-10

    6. [6]

      Jennifer Doudna and Emmanuelle Charpentier shared the 2020 Nobel Prize in Chemistry for developing CRISPR-Cas9 genome editing. confirmedas of 2026-10-10

    7. [7]

      Casgevy's approach edits a patient's blood stem cells outside the body by electroporating them with CRISPR-Cas9 aimed at an enhancer of the BCL11A gene, a gene that represses fetal hemoglobin, so that the cells make more fetal hemoglobin. confirmedas of 2026-10-10

    8. [8]

      In a 2021 NEJM study, NTLA-2001, a lipid nanoparticle carrying Cas9 mRNA and a guide RNA targeting the TTR gene, given by infusion, lowered blood TTR protein by a mean 87% at the 0.3 mg/kg dose, with mainly mild adverse events. confirmedas of 2026-10-10

    9. [9]

      Lonvo-z (lonvoguran ziclumeran) is Intellia's one-time, in vivo CRISPR/Cas9 treatment for hereditary angioedema, designed to permanently lower kallikrein by inactivating the KLKB1 gene, and given in an outpatient setting. confirmedas of 2026-10-10

    10. [10]

      In November 2025 CRISPR Therapeutics reported Phase 1 data, published in NEJM, for CTX310, an LNP-delivered CRISPR therapy that edits the ANGPTL3 gene in liver cells; at the highest dose mean ANGPTL3 fell 73%, triglycerides 55% and LDL cholesterol 49%, with no treatment-related serious adverse events reported. confirmedas of 2026-10-10

    11. [11]

      The HAELO Phase 3 trial randomized 80 patients 2:1 to a single 50 mg infusion of lonvo-z or placebo; median follow-up was 7.5 months as of 10 February 2026, and no serious or Grade 3 or higher adverse events were reported in the lonvo-z group. confirmedas of 2026-06-13

    12. [12]

      In the Phase 3 HAELO trial, a single infusion of lonvo-z reduced hereditary angioedema attacks by 87% versus placebo over weeks 5 to 28 (mean monthly attack rate 0.26 versus 2.10), and 62% of treated patients were attack-free and therapy-free versus 11% on placebo. confirmedas of 2026-10-10

    13. [13]

      At the European Society of Cardiology Congress on 28 August 2026, CRISPR Therapeutics reported one-year Phase 1a follow-up for CTX310, with mean reductions from baseline at the highest dose of 79% for ANGPTL3, 48% for triglycerides and 53% for LDL cholesterol, and said no additional treatment-related adverse events had occurred since the previous update; the data were published in NEJM the same day. confirmedas of 2026-08-28

    14. [14]

      In the published CTX310 Phase 1 trial, serious adverse events occurred in two of 15 participants (13%): one had a spinal disk herniation and the other died suddenly 179 days after treatment with the lowest, 0.1 mg per kilogram dose; the authors reported no dose-limiting toxic effects related to CTX310. confirmedas of 2025-11-08

    15. [15]

      On 29 October 2025 the FDA placed clinical holds on Intellia's Phase 3 MAGNITUDE and MAGNITUDE-2 trials of nex-z after a patient dosed in MAGNITUDE had Grade 4 liver transaminase elevations and increased bilirubin. confirmedas of 2026-10-10

    16. [16]

      The FDA lifted the clinical hold on Intellia's MAGNITUDE-2 trial in January 2026 and the hold on MAGNITUDE in March 2026, after the company agreed to study modifications including enhanced monitoring of liver laboratory tests; enrollment then advanced in both Phase 3 trials. confirmedas of 2026-08-06

    17. [17]

      In August 2026 Intellia said that a genomic analysis of more than 600 patient samples from nex-z trials, run with Regeneron and outside experts, found the highest observed liver transaminase elevations in patients carrying one specific HLA allele, and that it would give HLA genotyping results to investigators and to patients enrolled or entering screening in the ongoing Phase 3 trials. confirmedas of 2026-08-06

    18. [18]

      Base editing, reported in Nature in 2016, converts one DNA base into another in a programmable way without cutting both DNA strands, with typically 1% or fewer unwanted insertions or deletions in the original experiments. confirmedas of 2026-10-10

    19. [19]

      Prime editing, reported in Nature in 2019, pairs an impaired Cas9 with an engineered reverse transcriptase and a prime editing guide RNA (pegRNA) that both finds the target and encodes the edit, allowing insertions, deletions and all 12 kinds of single-base change without double-strand breaks or donor DNA. confirmedas of 2026-10-10

    20. [20]

      Casgevy's prescribing information carries warnings for neutrophil engraftment failure, delayed platelet engraftment, hypersensitivity reactions and off-target genome editing risk. confirmedas of 2026-10-10

    21. [21]

      Lipid nanoparticles can carry Cas9 mRNA and guide RNA into tissues, but reliably targeting tissues other than the liver remains a challenge. confirmedas of 2026-10-10

    22. [22]

      On 15 April 2026 the FDA published draft guidance recommending next-generation sequencing methods for the nonclinical safety assessment of genome editing in human gene therapy products, with comments due by 14 July 2026. confirmedas of 2026-10-10

    23. [23]

      As of August 2026, Casgevy was approved in 39 countries across North America, Europe and the Middle East. confirmedas of 2026-08-03

    24. [24]

      On 1 July 2026 the FDA expanded Casgevy's approval to patients aged 2 years and older with sickle cell disease or transfusion-dependent beta-thalassemia, 53 days after filing, under the Commissioner's National Priority Voucher pilot program. confirmedas of 2026-10-10

    25. [25]

      On 16 November 2023 the UK medicines regulator, the MHRA, authorised Casgevy for patients aged 12 and over with sickle cell disease or transfusion-dependent beta-thalassemia, the first authorisation of a CRISPR-based medicine. confirmedas of 2026-10-10

    26. [26]

      Adeno-associated virus (AAV) vectors carry a single-stranded DNA genome of about 4.7 kilobases, which limits cargo size, and their long-lasting expression of Cas9 may raise off-target risk. confirmedas of 2026-10-10

    Revision history (2)
    1. Page created.
    2. Added HAELO Phase 3 details, CTX310 one-year and safety data, the nex-z HLA finding and FDA sequencing guidance.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "CRISPR-Cas9." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/crispr-cas9

    Spotted an error? Suggest a correction or emailcorrections@contentlora.com.

    Keep exploring

    Connections
    Casgevy Basis forBase editing Extended byPrime editing Extended byLipid nanoparticle … Delivered in vivo byIntellia Therapeuti… Used byCRISPR Therapeutics Used by
    ☰ Contents