Gene Therapy Overview

Gene therapy is an innovative transformative treatment that restores, modifies, or enhances a person’s cellular functions through introduction of genetic material to ^treat or cure a disease . ^{(Nathwani et al, 2022)} The first gene therapies were approved by the Food and Drug Administration and European Medicines Agency in the 2010s,^{(Kymriah PI; Glybera SmPC)} with an increasing number of approvals, and more than 1100 active clinical trials ongoing across a range of diseases in recent times.(ClinicalTrials.gov search, 2021) Gene therapies work through a variety of approaches including functional gene transfer or gene inactivation/editing.(FDA What is Gene Therapy, 2018; Miesbach et al., 2019; Pasi, 2019) Approaches for inherited monogenic diseases have predominantly focused on the delivery of a functional gene using a viral vector, which can be divided into integrating (retrovirus, lentiviral) and non-integrating (adenovirus, adeno-associated virus [AAV]) vectors.(Prakash et al., 2016; Anguela and High, 2019) Gene therapies can be delivered either directly into the patient (in vivo gene therapy) or into cells extracted from the patient (ex vivo gene therapy).(High and Roncarolo, 2019; High and Roncarolo, 2019 supplementary graphic) A single, one-time administration of a gene therapy has been shown to have durable benefit to patients, although the long-term effects are yet to be fully characterized.(Nathwani et al., 2018; Maguire et al., 2019; Mendell et al., 2020; Mendell et al., MDA 2021; Konkle et al., 2021; FDA Guidance for Industry, 2021; EMA 2009