Question
Gene therapy
Answer
Gene therapy is the therapeutic approach of introducing, altering, or replacing genetic material within a patient’s cells to treat or prevent disease — either by correcting a defective/missing gene, by introducing a gene with a therapeutic function, or by silencing a harmful gene.
Types (by target cell):
- Somatic gene therapy — modifies genes only in the patient’s own somatic (body) cells; effects are limited to the treated individual and are not passed to offspring; this is the only form currently in clinical use.
- Germline gene therapy — would modify genes in reproductive cells/embryos, so changes would be heritable; raises major ethical concerns and is not currently permitted in clinical practice.
Approaches:
- Gene augmentation — introducing a normal, functional copy of a gene to compensate for a defective/absent gene (used in recessive single-gene disorders, e.g., SCID, haemophilia).
- Gene editing — direct correction of the mutant sequence using tools such as CRISPR-Cas9, zinc-finger nucleases, or TALENs.
- Gene silencing — using antisense oligonucleotides or RNA interference (siRNA) to switch off expression of a harmful/overactive gene.
- Suicide gene therapy — introducing a gene (e.g., herpes simplex thymidine kinase) that renders target cells (e.g., tumour cells) susceptible to a subsequently administered drug.
Vectors for gene delivery: viral vectors — retroviruses/lentiviruses (integrate into host genome, useful for stable long-term expression but carry insertional mutagenesis risk), adenoviruses and adeno-associated viruses (AAV, do not integrate, generally safer, widely used currently); non-viral methods — plasmid DNA with liposomes/lipid nanoparticles, or direct injection (“naked DNA”).
Clinical applications: severe combined immunodeficiency (SCID), certain inherited retinal disorders (e.g., Luxturna for RPE65-related blindness), haemophilia, spinal muscular atrophy, and as an adjunct in cancer therapy (e.g., CAR-T cell therapy, which involves genetically engineering a patient’s own T cells).
Limitations/challenges: risk of insertional mutagenesis (activation of oncogenes at the vector integration site), immune response against the viral vector, difficulty achieving durable/regulated expression, and high cost.