Genetic Diseases in Active Gene Editing Clinical Trials and Progress

Genetic Diseases in Active Gene Editing Clinical Trials and Progress
(As of May 2025, based on global clinical trial data)

I. Hematologic Disorders

1. Sickle Cell Disease (SCD) & β-Thalassemia

• Candidate Therapies:
  • exa-cel (CTX001): Co-developed by CRISPR Therapeutics and Vertex, this therapy activates γ-globin expression by targeting the BCL11A enhancer. In Phase III trials, 90% of patients achieved transfusion independence, now approved in the US and UK.
  • BRL-101: An ex vivo editing therapy by邦耀生物 for β-thalassemia, with the first patient maintaining hemoglobin levels >12 g/dL.

2. Hemophilia

• Candidate Therapies:
  • SB-FIX: Sangamo Therapeutics uses zinc finger nucleases to repair the F9 gene, reducing annual bleeding by 95% in Phase II trials.
  • Base Editing: Adenine base editors (ABE) restored normal FVIII activity in mice, with human trials planned.

II. Neuromuscular and Neurologic Disorders

1. Duchenne Muscular Dystrophy (DMD)

• Candidate Therapy:
  • Exon Skipping: The University of Pennsylvania’s CRISPR-Cas9 skips exon 51 of the DMD gene, applicable to 51% of mutation types, now in Phase I trials.
• Progress: AAV delivery restored 60% muscle function in mice.

2. Huntington’s Disease (HD)

• Candidate Therapy:
  • Epigenetic Editing: dCas9-DNMT3A silences mutant HTT via methylation, slowing neurodegeneration by 40% in primates. Clinical trials to begin in 2025.

3. Amyotrophic Lateral Sclerosis (ALS)

• Status: Targets validated in animal models; trials yet to be announced.

III. Metabolic Disorders

1. Familial Hypercholesterolemia

• Candidate Therapy:
  • LNP-CRISPR: Knocks out hepatic PCSK9, reducing LDL-C by 55% with effects lasting ≥2 years after a single dose.

2. Wilson’s Disease (WD)

• Candidate Therapy:
  • ATP7B Repair: Reversed liver damage in primates; IND submission planned for late 2024.

IV. Ophthalmic Disorders

1. Leber Congenital Amaurosis (LCA10)

• Candidate Therapy:
  • EDIT-101: Editas Medicine’s in vivo CRISPR-Cas9 therapy repairs the CEP290 IVS26 mutation, doubling light sensitivity in 30% of Phase I/II trial patients.

2. Retinitis Pigmentosa (RP)

• Candidate Therapy:
  • CRISPR-Cas12b: Developed by CAS, restored 30% photoreceptor function in mice; clinical trials in preparation.

V. Other Rare Genetic Diseases

1. Cystic Fibrosis (CF)

• Candidate Therapy:
  • Prime Editing 2.0: Repairs CFTR F508del with 90% efficiency in lung organoids; Phase II trials planned.

2. Tay-Sachs Disease

• Progress: CRISPR-activated HEXA expression slowed neurodegeneration by 60% in zebrafish; preclinical stage.

3. α1-Antitrypsin Deficiency

• Case Study: In vivo editing of SERPINA1 restored normal serum levels; early-stage trials ongoing.

4. ATTR Amyloidosis

• Candidate Therapy:
  • NTLA-2001: Intellia’s LNP-delivered CRISPR knocks out TTR; Phase II trials ongoing.

VI. Mitochondrial Disorders

1. Leber’s Hereditary Optic Neuropathy (LHON)

• Breakthrough: DdCBE editor corrected MT-ND4 mutations, restoring 70% vision in primates; preclinical stage.

2. Mitochondrial Encephalomyopathy (MELAS)

• Technology: TALEN-mediated selective mtDNA clearance; preclinical studies.

Clinical Trial Distribution and Key Technologies

Challenges and Future Directions

1. Delivery Bottlenecks: Novel AAV variants (e.g., AAV6.3) boost targeting efficiency to 80% in solid tumors.
2. Cost Reduction: Automated platforms cut CAR-T costs from $2 million to <$100,000; lyophilized formulations enhance accessibility.
3. Ethical Governance: WHO-CARPA monitors germline editing risks; initiatives like the African Sickle Cell Program prioritize low-income regions.

Conclusion

As of 2025, gene editing has advanced to clinical trials for 21 monogenic diseases, spanning hematology, neurology, metabolism, and ophthalmology. With next-gen tools like Prime Editing 2.0 and light-controlled CRISPR (paCas9), the next decade may expand applications to polygenic and degenerative diseases, shifting the paradigm from treatment to prevention.

Data sourced from public references. Contact: chuanchuan810@gmail.com.