Gene Therapy: Mechanisms, Clinical Translation, Challenges, and Future Perspectives
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https://doi.org/10.69760/portuni.26050007##semicolon##
Gene therapy##common.commaListSeparator## adeno-associated virus##common.commaListSeparator## lentiviral vectors##common.commaListSeparator## CRISPR-Cas9##common.commaListSeparator## base editing##common.commaListSeparator## prime editing##common.commaListSeparator## CAR-T cell therapy##common.commaListSeparator## lipid nanoparticles##common.commaListSeparator## insertional mutagenesis##common.commaListSeparator## precision medicineSantrauka
Gene therapy has progressed from a speculative concept to a clinically validated therapeutic modality, transforming the management of monogenic disorders, hematologic malignancies, and ocular, neuromuscular, and cardiovascular diseases. Following nearly five decades of preclinical refinement and a turbulent early clinical history marked by serious adverse events, the field has matured into a regulated discipline supported by over 3,900 clinical trials worldwide. This review synthesizes the current state of gene therapy, with emphasis on viral and non-viral delivery platforms—particularly adeno-associated viral (AAV) vectors, lentiviral vectors, and ionizable lipid nanoparticles (LNPs)—as well as somatic versus germline and in vivo versus ex vivo classifications. Landmark regulatory approvals, including voretigene neparvovec (Luxturna), onasemnogene abeparvovec (Zolgensma), etranacogene dezaparvovec (Hemgenix), exagamglogene autotemcel (Casgevy), and chimeric antigen receptor (CAR)-T cell therapies, are critically appraised. Genome-editing innovations—CRISPR-Cas9, base editing, and prime editing—are discussed in the context of expanding therapeutic precision. Persistent challenges encompass immunogenicity, off-target editing, insertional mutagenesis, durability of expression, manufacturing scalability, and equitable access. The review concludes with future perspectives on next-generation vectors, in vivo CAR-T engineering, and global access frameworks essential to realizing the curative promise of genetic medicine.
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