Genome editing

01Overview and value chain#

Markers EC: FDA Gene-Therapy Guidance & RMAT designation, EMA ATMP Regulation | OECD: bio-pharma | Regulator: FDA (US), EMA (EU), NMPA (CN)

Genome editing rewrites DNA in living cells with programmable nucleases — CRISPR-Cas9, base editors and prime editors — to treat genetic disease, engineer cells and build biological platforms. CRISPR Therapeutics’ Casgevy, the first approved CRISPR therapy, edits autologous CD34+ stem cells ex vivo to induce fetal hemoglobin, with Phase 3 CLIMB-151 showing 73% of treated children free of vaso-occlusive crises for at least 12 months (median about 19 months) and the FDA now reviewing expansion to children as young as 5. Intellia’s in-vivo lipid-nanoparticle-delivered CRISPR (NTLA-2001) achieved a median 52% reduction in serum TTR, and redosing reached a 90% median knockdown at day 28 — the first clinical redosing of an in-vivo CRISPR therapy. Base editing has moved into cardiovascular care: Lilly/Verve’s VERVE-102 cut PCSK9 by up to 88% and LDL-C by up to 62% from a single infusion (NEJM). Prime editing (“search-and-replace”) now reaches the liver in vivo via all-RNA LNP platforms, covering the vast majority of known disease-causing mutations.

The key directions of genome editing are:

1. Ex-vivo CRISPR-Cas9 cell therapy (CRISPR-Cas9 Cell Therapy): Casgevy edits autologous hematopoietic stem cells to induce fetal hemoglobin for sickle cell disease and beta-thalassemia, now expanding to younger patients.
2. In-vivo CRISPR via LNP delivery (In-vivo CRISPR): Intellia’s NTLA-2001 (ATTR amyloidosis) and lonvo-z (hereditary angioedema, rolling BLA in 2026) enable one-time, redosable outpatient editing.
3. Base editing (Base Editing): Beam’s BEAM-304 (PKU), BEAM-302 (AATD) and BEAM-101 (SCD), plus Verve/Lilly’s VERVE-102, which cut LDL-C by up to 62% from a single PCSK9 edit.
4. Prime editing & search-and-replace (Prime Editing): Prime Medicine and the Broad Institute advance precise substitutions and small indels, with all-RNA LNP delivery enabling in-vivo prime editing and an AI-redesigned reverse transcriptase.

Sectoral value chain#

[Target & guide design] ──> [Editor engineering] ──> [Delivery] ──> [Editing & selection]
                                  │
                          (LNP / viral / electroporation)
                                  │
                                  ▼
[Approved gene medicine] <─── [Clinical & regulatory] <─── [Manufacturing]

Value chain levels#

Cross-cutting technologies of the sector:

• CRISPR-Cas9 & base/prime editors (Editing Modalities): the three editor classes that define what DNA change is possible — cuts, single-base swaps, precise substitutions.
• Lipid-nanoparticle & viral delivery (Delivery): LNP (mRNA + guide) and viral vectors that carry editors into cells and organs, especially the liver.
• AI-assisted editor design (AI Editor Design): machine-learning redesign of editor enzymes (e.g. reverse transcriptase) to boost stability, abundance and potency.

02US#

The United States concentrates the genome-editing pipeline, spanning in-vivo CRISPR, base editing, prime editing and cardiovascular base editing, under the FDA’s Regenerative Medicine Advanced Therapy (RMAT) pathway.

in-vivo CRISPR, base editing, prime editing, cardiovascular base editing#

• Intellia Therapeutics (Cambridge, MA): in-vivo LNP-delivered CRISPR — NTLA-2001 for ATTR amyloidosis (first clinical redosing of an in-vivo CRISPR therapy) and lonvo-z for hereditary angioedema, with a rolling BLA submission underway in 2026.
• Beam Therapeutics (Cambridge, MA): base editing platform — BEAM-304 (PKU, IND clearance June 2026), BEAM-302 (AATD) and BEAM-101 (SCD, all patients reaching HbF >60%).
• Prime Medicine & Verve Therapeutics: prime editing moving in vivo via all-RNA LNP platforms, and Verve’s VERVE-102 (now under Eli Lilly) cutting LDL-C by up to 62% from a single PCSK9 base edit.
• Editas Medicine (Cambridge, MA): transitioned in December 2024 from ex-vivo CRISPR-Cas12a (reni-cel, discontinued) to in-vivo gene editing; lead candidate EDIT-401 upregulates LDLR and cut LDL-C, Lp(a) and ApoB by ~90% in non-human primates, IND/CTA targeted for mid-2026.
• Caribou Biosciences (Berkeley, CA): chRDNA (hybrid DNA/RNA guide) CRISPR for off-the-shelf allogeneic cell therapy — CB-010 anti-CD19 CAR-T.
• Tessera Therapeutics: Gene Writing platform using engineered mobile genetic elements to write therapeutic sequences into the genome (preclinical platform).
• Scribe Therapeutics (Berkeley, CA): engineered CasX (X-edit) CRISPR platform, partnered with Sanofi on in-vivo editing.

03CN#

China is building a domestic genome-editing therapy pipeline under the NMPA, with EdiGene’s beta-thalassemia program the first gene-editing therapy cleared for a clinical trial in the country.

China CRISPR therapeutics, beta-thalassemia, NMPA-cleared trials#

• EdiGene (博雅辑因, Beijing): ET-01, a gene-editing therapy for beta-thalassemia, was the first gene-editing therapy cleared for a clinical trial by the NMPA’s Center for Drug Evaluation.
• CorrectSequence Therapeutics (Shanghai): CS-101, a base-editing therapy for beta-thalassemia reported in Nature, reduced patients’ need for blood transfusions within weeks.
• NMPA regulatory framework: the Center for Drug Evaluation’s gene-therapy review pathway anchors a growing pipeline of domestic CRISPR and base-editing candidates.

04EU#

Europe anchors the field’s commercial milestone — CRISPR Therapeutics’ Casgevy, the first approved CRISPR therapy — and pushes CRISPR beyond human therapy into microbiome editing under the EMA’s Advanced Therapy Medicinal Products (ATMP) framework.

approved CRISPR therapy, microbiome editing#

• CRISPR Therapeutics (Zug, Switzerland): Casgevy (exagamglogene autotemcel), the first approved CRISPR-Cas9 therapy, for sickle cell disease and transfusion-dependent beta-thalassemia; the FDA is reviewing expansion to children as young as 5 after Phase 3 CLIMB-151 data (73% VOC-free ≥12 months).
• Eligo Bioscience (Paris): CRISPR-engineered phage and phage-derived capsid particles that deliver base editors and CRISPR payloads to gut bacteria in situ, enabling in-vivo microbiome editing.
• EMA ATMP pathway: the advanced-therapy regulatory route governing gene-editing medicines across the EU.

05Leading companies and research institutes#

06Tech stack and innovations#

The genome-editing stack spans three editor classes and a delivery toolbox that is moving the field from one-time ex-vivo cures toward redosable, in-vivo medicines.

1. CRISPR-Cas9 & ex-vivo cell editing (CRISPR-Cas9):
   • Casgevy edits autologous CD34+ hematopoietic stem cells ex vivo, disrupting the BCL11A erythroid enhancer to reactivate fetal hemoglobin; Phase 3 CLIMB-151 shows 73% of children VOC-free for ≥12 months.
   • Electroporation delivers the editor into harvested cells, which are reinfused after editing and expansion.
2. Base & prime editing (Base & Prime Editing):
   • Adenine/cytosine base editors swap single bases without double-strand breaks — Beam’s BEAM-304 (PKU) and Lilly/Verve’s VERVE-102, which cut PCSK9 by up to 88% and LDL-C by up to 62% from one infusion.
   • Prime editors write precise substitutions and small indels (“search-and-replace”); all-RNA LNP platforms and an AI-redesigned reverse transcriptase now enable in-vivo prime editing in the liver.
3. In-vivo delivery & microbiome editing (Delivery & Microbiome):
   • Lipid-nanoparticle delivery carries mRNA editors plus guides in vivo — Intellia’s NTLA-2001 achieved the first clinical redosing of an in-vivo CRISPR therapy (90% median TTR knockdown on redose).
   • Eligo’s CRISPR-engineered phage capsid particles deliver base editors to gut bacteria in situ, extending genome editing to the microbiome.

07Value chains and production pipelines#

Industrial pipeline of genome-editing therapy development (FDA RMAT / EMA ATMP)#

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Target & guide design  │ ───> │ 2. Editor engineering     │
└───────────────────────────┘      └───────────────────────────┘
                                                  │
                                                  ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Editing & selection    │ <─── │ 3. Delivery               │
└───────────────────────────┘      └───────────────────────────┘
               │
               ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Manufacturing           │ ───> │ 6. Clinical & regulatory  │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Target & guide design

A disease-causing gene is selected and a guide RNA (plus editor architecture) is designed against the target locus, using the reference genome and predictive models of editing efficiency and off-target risk.

Stage 2: Editor engineering

The Cas9, base or prime editor is optimized — including AI-assisted redesign of components such as the reverse transcriptase — and packaged as mRNA plus chemically modified guide RNA.

Stage 3: Delivery

The payload is delivered ex vivo into harvested cells by electroporation, or in vivo to the patient via lipid nanoparticles (often GalNAc-conjugated for liver targeting) or viral vectors.

Stage 4: Editing & selection

For ex-vivo therapies the desired edit is confirmed and the edited cell population (e.g. CD34+ stem cells) is selected and expanded; for in-vivo therapies, editing is confirmed via circulating biomarkers (TTR, PCSK9, kallikrein).

Stage 5: Manufacturing

Clinical-grade drug substance and product are manufactured — autologous edited cell products under GMP cell-processing, or LNP-mRNA drug product under aseptic fill-finish.

Stage 6: Clinical & regulatory

Trials run under accelerated pathways (FDA RMAT, EMA ATMP, NMPA gene-therapy review) toward a marketing authorization, exemplified by Casgevy’s approvals and Intellia’s rolling BLA for lonvo-z in 2026.