# Genome editing

Programmable genome editors — CRISPR-Cas9, base editors and prime editors — delivered ex vivo or in vivo via lipid nanoparticles to treat genetic disease, from the first approved CRISPR therapy Casgevy to in-vivo redosable CRISPR and single-dose cardiovascular base editing.

Source: https://en.bioecon.ru/technology/genome-editing/
Updated: 2026-09-02



## Overview 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

| Level | Description | Key inputs/outputs |
|:---|:---|:---|
| **Target & guide design** | A disease gene is selected and a guide RNA / editor architecture is designed against it | **In:** Disease gene, reference genome.<br>**Out:** Guide RNA, editor design. |
| **Editor & payload engineering** | The Cas9 / base / prime editor is optimized and packaged as mRNA + guide | **In:** Guide RNA, editor protein.<br>**Out:** mRNA editor + guide payload. |
| **Delivery** | Payload is delivered ex vivo (electroporation) or in vivo (LNP, viral) | **In:** Payload, patient cells.<br>**Out:** Edited cells or dosed patient. |
| **Editing & selection** | Cells are edited and, for ex-vivo therapies, the desired edit is selected/expanded | **In:** Delivered payload.<br>**Out:** Edited cell population. |
| **Manufacturing** | Clinical-grade drug substance and product are produced (viral/LNP/cell therapy) | **In:** Edited cells or mRNA payload.<br>**Out:** Clinical-grade therapy. |
| **Clinical & regulatory** | Trials run under RMAT/ATMP pathways to a marketing authorization | **In:** Clinical-grade therapy.<br>**Out:** FDA/EMA/NMPA-approved gene medicine. |

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.

---

## US

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.

---

## CN

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.

---

## EU

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.

---

## Leading companies and research institutes

| Company / Institute | Country | Key products / platforms | Tech features | Status 2026 |
|:---|:---|:---|:---|:---|
| **CRISPR Therapeutics** | 🇨🇭 Switzerland | *Casgevy (CRISPR-Cas9)* | First approved CRISPR therapy; SCD/TDT | commercial |
| **Intellia Therapeutics** | 🇺🇸 USA | *In-vivo CRISPR (LNP)* | NTLA-2001 ATTR; lonvo-z HAE BLA 2026 | commercial |
| **Beam Therapeutics** | 🇺🇸 USA | *Base-editing platform* | BEAM-304 PKU; BEAM-302 AATD | clinical |
| **Prime Medicine** | 🇺🇸 USA | *Prime editing (search-and-replace)* | In-vivo LNP prime editing | clinical |
| **Verve Therapeutics** | 🇺🇸 USA | *Cardiovascular base editing* | VERVE-102 PCSK9 −62% LDL-C (Lilly) | clinical |
| **EdiGene** | 🇨🇳 China | *China CRISPR therapeutics* | ET-01 β-thalassemia (first NMPA-cleared) | clinical |
| **Editas Medicine** | 🇺🇸 USA | *in-vivo CRISPR therapeutics* | EDIT-401 LDLR upregulation; IND mid-2026 | preclinical |
| **Caribou Biosciences** | 🇺🇸 USA | *chRDNA CRISPR* | CB-010 allogeneic CAR-T | clinical |
| **Tessera Therapeutics** | 🇺🇸 USA | *Gene Writing platform* | mobile-element insertional editing | clinical |
| **Scribe Therapeutics** | 🇺🇸 USA | *CasX X-edit platform* | engineered CasX, Sanofi partnership | clinical |

---

## Tech 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.

---

## Value 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.