Cell and Gene Therapies: Emerging Pharmacotherapeutic Strategies for Rare Diseases

Abstract

Rare diseases are individually uncommon but collectively impose substantial clinical, social and economic burdens. Many are monogenic disorders in which a pathogenic variant disrupts a protein, enzyme, structural component or regulatory pathway. Cell and gene therapies (CGTs) offer the possibility of addressing disease mechanisms more directly than conventional symptom-directed pharmacotherapy. Therapeutic strategies include in vivo gene addition using viral or non-viral vectors; ex vivo genetic modification of autologous haematopoietic stem and progenitor cells; genome editing; and cell replacement or engineered-cell approaches. Clinical translation has progressed from proof-of-concept studies to authorised products for selected disorders, including spinal muscular atrophy, inherited retinal dystrophy, haemophilia B, metachromatic leukodystrophy, sickle cell disease and transfusion-dependent β-thalassaemia in certain jurisdictions. However, the evidence, eligibility criteria, durability and benefit-risk profile differ by product and disease. Important constraints include immune responses, off-target or insertional effects, conditioning toxicity, manufacturing complexity, limited long-term data, high costs and unequal access. This narrative review summarises the biological rationale, platforms, representative clinical evidence, clinical implementation, safety, regulatory considerations and emerging directions in rare-disease CGTs, with attention to the Indian context. It emphasises multidisciplinary care, transparent communication and long-term pharmacovigilance.

Keywords

Authors & affiliations

Cite this article

Shruti Patel. Cell and Gene Therapies: Emerging Pharmacotherapeutic Strategies for Rare Diseases. ClinSphere Journals. 2026;undefined(undefined). https://doi.org/10.5281/zenodo.23806863

1. U.S. Food and Drug Administration. Cellular & Gene Therapy Products. Silver Spring (MD): FDA; current product information. Available from: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products
2. U.S. Food and Drug Administration. Long Term Follow-Up After Administration of Human Gene Therapy Products: Guidance for Industry. Silver Spring (MD): FDA; 2020. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/long-term-follow-after-administration-human-gene-therapy-products
3. Day JW, Finkel RS, Chiriboga CA, Connolly AM, Crawford TO, Darras BT, et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Lancet Neurol. 2021;20(4):284-293. doi:10.1016/S1474-4422(21)00001-6.
4. Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390(10097):849-860. doi:10.1016/S0140-6736(17)31868-8.
5. Pipe SW, Leavitt AD, Ragni MV, Tarantini F, Ewenstein B, Iorio A, et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med. 2023;388:706-718. doi:10.1056/NEJMoa2211644.