// Therapies

The genetic-medicine pharmacopoeia

Approved and pivotal-trial-stage drugs that act on, deliver, or rewrite nucleic acids — from CRISPR and base editors through siRNA, ASO, mRNA, AAV, and engineered cell therapies. Snapshot reflects the 2024–2026 landscape.

Casgevy

(exa-cel)Approved

CRISPR-Cas9 ex-vivo HSC · target BCL11A erythroid enhancer

Indication: Severe sickle cell disease, transfusion-dependent β-thalassemia

First approved CRISPR therapy (Dec 2023). ~$2.2M list. Reactivates fetal hemoglobin via enhancer disruption.

Sponsor

Vertex / CRISPR Tx

Pivotal ref

Lyfgenia

(lovo-cel)Approved

Lentiviral ex-vivo HSC · target βA-T87Q globin

Indication: Severe sickle cell disease

Approved alongside Casgevy (Dec 2023). Black-box for hematologic malignancy.

Sponsor

bluebird bio

Zolgensma

(onasemnogene abeparvovec)Approved

AAV9 in-vivo gene replacement · target SMN1

Indication: Spinal muscular atrophy (≤2 years)

Single-dose IV; greatest benefit pre-symptomatic (SPR1NT).

Sponsor

Novartis

Luxturna

(voretigene neparvovec)Approved

AAV2 subretinal · target RPE65

Indication: Biallelic RPE65 retinal dystrophy

First in-vivo AAV gene therapy approved in the US (2017).

Sponsor

Spark

Hemgenix

(etranacogene dezaparvovec)Approved

AAV5 · target F9 (Padua)

Indication: Hemophilia B

Single IV infusion; durability and re-dosing remain open questions.

Sponsor

CSL Behring / uniQure

Roctavian

(valoctocogene roxaparvovec)Approved

AAV5 · target F8

Indication: Hemophilia A

Approved 2022 EU / 2023 US; expression wanes over years.

Sponsor

BioMarin

Elevidys

(delandistrogene moxeparvovec)Approved

AAVrh74 · target Micro-dystrophin

Indication: Duchenne muscular dystrophy

Accelerated then full FDA approval; functional benefit signals modest, ongoing controversy.

Sponsor

Sarepta

Spinraza

(nusinersen)Approved

Splice-switching ASO (intrathecal) · target SMN2 exon 7

Indication: Spinal muscular atrophy

Quarterly intrathecal dosing; competitor to Zolgensma.

Sponsor

Biogen / Ionis

Patisiran

(Onpattro)Approved

LNP siRNA (IV) · target TTR

Indication: hATTR polyneuropathy

First approved siRNA drug (2018).

Sponsor

Alnylam

Vutrisiran

(Amvuttra)Approved

GalNAc-siRNA (SC) · target TTR

Indication: hATTR polyneuropathy / cardiomyopathy

Quarterly SC dosing; cardiomyopathy expansion 2024 (HELIOS-B).

Sponsor

Alnylam

Inclisiran

(Leqvio)Approved

GalNAc-siRNA · target PCSK9

Indication: Hypercholesterolemia, ASCVD risk reduction

Twice-yearly SC; ~50% LDL-C reduction (ORION program).

Sponsor

Novartis

Givosiran

(Givlaari)Approved

GalNAc-siRNA · target ALAS1

Indication: Acute hepatic porphyria

Monthly SC; reduces porphyric attacks.

Sponsor

Alnylam

Lumasiran

(Oxlumo)Approved

GalNAc-siRNA · target HAO1

Indication: Primary hyperoxaluria type 1

Pediatric and adult use.

Sponsor

Alnylam

Eplontersen

(Wainua)Approved

GalNAc-ASO (SC) · target TTR

Indication: hATTR polyneuropathy

Monthly SC autoinjector.

Sponsor

Ionis / AstraZeneca

Kymriah / Yescarta / Tecartus / Breyanzi

Approved

Autologous CD19 CAR-T · target CD19

Indication: B-cell malignancies

First-line lymphoma data continues to expand.

Sponsor

Novartis / Kite / BMS

Abecma / Carvykti

Approved

Autologous BCMA CAR-T · target BCMA

Indication: Multiple myeloma

Carvykti now moving to earlier line (CARTITUDE-4).

Sponsor

BMS / J&J–Legend

NTLA-2001

Phase 3

LNP CRISPR-Cas9 (in vivo, IV) · target TTR

Indication: ATTR amyloidosis (PN + CM)

First systemic in-vivo CRISPR; ~90% sustained TTR knockdown after single dose.

Sponsor

Intellia / Regeneron

Pivotal ref

VERVE-102

Phase 1/2

LNP base editor (ABE, in vivo) · target PCSK9

Indication: Heterozygous familial hypercholesterolemia / ASCVD

Re-engineered LNP after VERVE-101 ALT signal; first base-editor cardiovascular program.

Sponsor

Verve Therapeutics

VERVE-201

Phase 1/2

GalNAc-LNP base editor · target ANGPTL3

Indication: HoFH, refractory hyperlipidemia

GalNAc-targeted hepatic delivery.

Sponsor

Verve Therapeutics

EDIT-301 / Reni-cel

Phase 1/2

Cas12a ex-vivo HSC · target HBG1/2 promoter

Indication: Sickle cell disease, β-thalassemia

Alternative HbF-reactivation strategy to Casgevy.

Sponsor

Editas Medicine

BEAM-101

Phase 1/2

Base editor ex-vivo HSC · target HBG promoter

Indication: Sickle cell disease

First clinical base-editor program.

Sponsor

Beam Therapeutics

CTX112 / CTX131

Phase 1/2

Allogeneic CRISPR CAR-T · target CD19 / CD70

Indication: B-cell, autoimmune, solid tumors

Multiple-edit allogeneic platform.

Sponsor

CRISPR Therapeutics

mRNA-4157

(intismeran autogene)Phase 3

Personalized neoantigen mRNA vaccine · target Patient-specific neoantigens

Indication: Resected high-risk melanoma (+ pembrolizumab)

KEYNOTE-942 phase 2 HR ~0.56 for RFS; phase 3 INTerpath ongoing.

Sponsor

Moderna / Merck

BNT122 / autogene cevumeran

Phase 1/2

Personalized neoantigen mRNA vaccine · target Patient-specific neoantigens

Indication: Pancreatic, colorectal

Striking T-cell + RFS signal in resected PDAC (Rojas Nature 2023).

Sponsor

BioNTech / Genentech

CABA-201

Phase 1/2

Autologous CD19 CAR-T · target CD19

Indication: Refractory autoimmune (SLE, myositis, SSc)

Following Schett group case-series approach.

Sponsor

Cabaletta Bio

Capstan CPTX-2309

Phase 1/2

In-vivo CAR-T via tCD8-LNP · target CD19 (in vivo)

Indication: B-cell autoimmunity

Eliminates autologous manufacturing burden if safe.

Sponsor

Capstan Therapeutics