What is Gene Therapy?

Gene therapy is a biomedical technique that modifies or manipulates genes to treat or prevent disease. It involves introducing, removing, or altering genetic material within a patient’s cells to correct faulty genes or to make beneficial proteins.

Key Approaches

  1. Gene Addition: Inserting a healthy copy of a gene to compensate for a defective one.
  2. Gene Editing: Precisely changing specific DNA sequences (e.g., using CRISPR-Cas9).
  3. Gene Silencing: Turning off malfunctioning genes (e.g., using RNA interference).
  4. Gene Replacement: Swapping a faulty gene with a functional version.

Delivery Methods

  • Viral Vectors: Modified viruses deliver genetic material into cells (e.g., adenovirus, lentivirus).
  • Non-viral Methods: Includes liposomes, nanoparticles, and direct injection of DNA/RNA.
  • Ex vivo vs. In vivo:
    • Ex vivo: Cells are modified outside the body and then returned.
    • In vivo: Genes are delivered directly into the patient.

How CRISPR Works

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a revolutionary gene-editing tool. It uses a guide RNA to direct the Cas9 enzyme to a specific DNA sequence, where it makes a cut. The cell then repairs the DNA, allowing scientists to add, delete, or correct genes with high precision.

CRISPR Diagram

Applications

  • Inherited Disorders: Sickle cell anemia, cystic fibrosis, hemophilia.
  • Cancer: Engineering immune cells (CAR-T therapy) to target tumors.
  • Infectious Diseases: Research into HIV, hepatitis, and COVID-19 gene therapies.
  • Rare Diseases: Addressing conditions with no other treatments.

Latest Discoveries

  • Prime Editing (2020): A new CRISPR-based technique that enables even more precise DNA changes, reducing off-target effects.
  • In Vivo CRISPR Trials (2021): First successful use of CRISPR inside the human body to treat transthyretin amyloidosis (NTLA-2001 trial).
  • Base Editing (2022): Allows single-letter changes in DNA, opening doors for correcting point mutations.
  • Epigenome Editing: Modifies gene expression without altering DNA sequence.

Cited Study:
Gillmore, J.D., et al. (2021). CRISPR–Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. New England Journal of Medicine, 385(6), 493-502. Link

Global Impact

  • Healthcare Equity: Gene therapy has the potential to cure previously untreatable diseases, but access remains limited by cost and infrastructure.
  • Regulatory Approvals: Dozens of gene therapies have been approved in the US, EU, and Asia for rare diseases and cancers.
  • Ethical Considerations: Germline editing (editing embryos) is controversial and mostly banned, while somatic cell therapy is widely accepted.
  • Economic Growth: The gene therapy market is projected to exceed $20 billion by 2027, driving biotech innovation worldwide.

Surprising Facts

  1. First In Vivo CRISPR Success: In 2021, scientists edited genes inside a living human for the first time, reducing disease-causing protein levels by 87%.
  2. Gene Therapy for Blindness: Luxturna, approved in 2017, can restore vision in patients with a rare inherited eye disease.
  3. Ultra-Rare Disease Treatments: Some gene therapies are developed for diseases affecting fewer than 10 people worldwide, using personalized approaches.

Diagrams

Gene Therapy Process

Gene Therapy Process

Viral Vector Delivery

Viral Vector Delivery

Glossary

  • Allele: Variant form of a gene.
  • Base Editing: Technique to change a single DNA base (A, T, C, G) without cutting both DNA strands.
  • CRISPR: Gene-editing technology using a guide RNA and Cas9 enzyme for targeted DNA modification.
  • Ex vivo: Outside the living body.
  • Germline Cells: Reproductive cells (sperm, eggs) that pass genetic information to offspring.
  • In vivo: Inside the living body.
  • Somatic Cells: All body cells except germline cells.
  • Vector: Vehicle for delivering genetic material into cells.

Ethical and Safety Concerns

  • Off-target Effects: Unintended genetic changes may cause side effects.
  • Long-term Effects: Unknown risks over decades.
  • Consent: Especially complex for children and unborn individuals.
  • Regulation: Varies by country; strict oversight is required.

Future Directions

  • Personalized Gene Therapy: Tailoring treatments to individual genetic profiles.
  • Gene Therapy for Common Diseases: Expanding to diabetes, heart disease, and neurodegenerative disorders.
  • Global Access Initiatives: Efforts to make therapies affordable and available worldwide.
  • Synthetic Biology: Designing entirely new genes for therapeutic use.

References

  • Gillmore, J.D., et al. (2021). CRISPR–Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. NEJM, 385(6), 493-502. Read
  • National Institutes of Health. Gene Therapy
  • Nature Reviews Genetics (2023). Advances in Genome Editing.