Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5397_Библиотеки_им_академика_М_И_Перельмана

transfer. A decade following the initial observation that bacteriophages possess the ability to transfer genetic material between bacteria, Howard Temin made a signi­cant discovery that demonstrated the inheritance of specic genetic changes through viral infection. The researcher reached the conclusion that chicken cells that have been infected with the Rous sarcoma virus (RSV) exhibited stable inheritance of viral-specic gene changes, which included the necessary information for the pro­duction of RSV progeny, based on his experimental observations. The enormous therapeutic potential of introducing DNA sequences into patients’ cells to address hereditary disorders was highlighted by renowned scientists Theodore Friedmann and Richard Roblin. Nearly 18years after considerable study on gene therapy pros­pects, the retrovirus was used to generate a neomycin-resistant marker on tumor­inltrating lymphocytes so that inltrating lymphocytes could be detected in melanoma treatment. The rst clinical experiment employing gene therapy was per­formed to treat severe combined immunodeciency (SCID) disorder, which is caused by a defective adenosine deaminase (ADA) gene. In 1990, to treat a 4-year­old kid, a functioning copy of the adenosine deaminase (ADA) gene using a viral vector was injected. The success of this clinical trial showcased the possibility of gene therapy. The success of the above-mentioned trial also paved the way for many trials in the gene therapy eld (Wirth etal. 2013). However, severe adverse effects were also reported while employing vectors of viral origin. These vectors apart from the severe adverse effects also caused immunological reactions as well as inser­tional mutagenesis. These incidents did hinder the advancement of this type of ther­apy. In 2000, a clinical trial was conducted in Paris for X-linked severe combined immunodeciency, which is caused by mutations in the IL2RG gene located in the X chromosome. The vector employed to carry the normal copy of the gene induced the oncogene resulting in leukemia in 5 out of 20 infants who received treatment. In a separate gene therapy trial done in London, Thrasher and colleagues reported an additional instance of leukemia following retroviral-mediated gene therapy for SCID.An unfortunate case of death of an 18-year old happened in 1999 who was diagnosed with ornithine transcarbamylase deciency and volunteered for the orni­thine transcarbamylase gene encoding adenoviral vector gene transfer trial. While these setbacks hindered the progress of gene therapy, they also revealed the promis­ing future and potential of this therapeutic approach. Many gene therapy products were approved for the treatment of various disorders. The rst gene therapy product to receive regulatory approval was Gendicine, approved in China in 2003 for the treatment of head and neck squamous cell carcinoma. Following this, Strimvelis gained conditional marketing authorization from the European Medicines Agency (EMA) in 2016 for the treatment of severe combined immunodeciency. In 2017, the USFDA approved Kymriah, a chimeric antigen receptor T-cell (CAR-T) ther­apy, for pediatric and young adult patients with relapsed or refractory acute lympho­blastic leukemia (ALL). Later in 2017, the FDA also approved Luxturna for the treatment of inherited retinal dystrophy caused by mutations in the RPE65 gene. Zolgensma, a gene therapy for spinal muscular atrophy (SMA), received FDA approval in 2019. These approvals represent signicant milestones in the evolving eld of gene therapy, showcasing its potential for treating a range of genetic and