text: Gene therapy is a medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.
  The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989. The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I. In 2003, Gendicine became the first gene therapy to receive regulatory approval. Since that time, further gene therapy drugs were approved, such as Glybera (2012), Strimvelis (2016), Kymriah (2017), Luxturna (2017), Onpattro (2018), Zolgensma (2019), Abecma (2021), Adstiladrin, Roctavian and Hemgenix (all 2022). Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. AAVs are characterized by stabilizing the viral capsid, lower immunogenicity, ability to transduce both dividing and nondividing cells, the potential to integrate site specifically and to achieve long-term expression in the in-vivo treatment. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.
  Not all medical procedures that introduce alterations to a patient's genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.