Gene therapy clinical trials worldwide to 2012—An update

Gene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Locked Bag 23, Wentworthville, NSW, 2145, Australia
The Journal of Gene Medicine (Impact Factor: 2.47). 02/2013; 15(2). DOI: 10.1002/jgm.2698
Source: PubMed

ABSTRACT To date, over 1800 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical trials from official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our June 2012 update, we have entries on 1843 trials undertaken in 31 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: We also provide an overview of the progress being made in clinical trials of gene therapy approaches around the world and discuss the prospects for the future. Copyright © 2013 John Wiley & Sons, Ltd.

Download full-text


Available from: Samantha L Ginn, Aug 28, 2015
  • Source
    • "Alternate non-viral vectors can be suggested for the development of " artificial viruses " synthetic polycations that equal viral counterparts in terms of their transfection efficacy, while being much safer, targetcell specific, non-immunogenic and relatively inexpensive to prepare at scales that permit clinical use [2]. However, despite a significant progress in development of novel carrier systems, only a limited number has been successfully tested in primary cells or in animal models and thus became appropriate for future clinical trials [3]. In general, the efficacy of non-viral carriers remains low. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Absence of safe and efficient methods of nucleic acids delivery is one of the major issues which limits the development of human gene therapy. Highly efficient viral vectors raise questions due to safety reasons. Among non-viral vectors peptide-based carriers can be considered as good candidates for the development of " artificial viruses "-multifunctional polyplexes that mimic viruses. Suggested strategy to obtain multifunctionality is to combine several peptide modules into one modular carrier. Different kinds of peptide modules are needed for successful overcoming barriers of nucleic acids transport into the cells. Design of such modules and establishment of structure-function relationships are issues of importance to researchers working in the field of nucleic acids delivery.
    Current Topics in Medicinal Chemistry 02/2016; 16(2):1-13. · 3.45 Impact Factor
  • Source
    • "Due to their high capacity for infection, the majority of clinical trials conducted to date are based on these viral vectors. Since the first clinical assay in 1989, ~2142 clinical evaluations have been conducted [4], [ wileychi/genmed/clinical/]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nucleic acid delivery constitutes an emerging therapeutic strategy to cure various human pathologies. This therapy consists of introducing genetic material into the whole body or isolated cells to correct a cellular abnormality or disfunction. As with any drug, the main objective of nucleic acid delivery is to establish optimal balance between efficacy and tolerance. The methods of administration and the vectors used are selected depending on whether the goal of treatment is the production of an active protein; the replacement of a missing or inactive gene; or the combat of acquired diseases, such as cancer or AIDS. In that sense, synthetic vectors represent a valuable solution because they are well characterized, their structure can be fine tuned, and their potential toxicity can be reduced, since toxicity depends on the composition of the formulations. Here we review various synthetic vectors for gene delivery and address the question of their biodistribution as a function of the route of administration. We highlight the modifications to vectors structure and formulations necessary to overcome the major hurdles limiting the effectiveness of nucleic acid therapies. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Biotechnology Journal 06/2015; DOI:10.1002/biot.201400841 · 3.71 Impact Factor
  • Source
    • "Ad vectors are one of the most efficient gene transfer systems in vivo [1], representing delivery vehicles in 23.5% of human gene therapy trials which are presently being performed worldwide [31]. One of the limitations to be considered while using Ad vectors is the adaptive and innate immune responses evoked against the Ad capsid or intracellularly expressed Ad gene products [32] [33]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Adenovirus vector is one of the most widely used vectors in gene therapy applications for the treatment of diverse human diseases including cancer. In this study, we showed that infection with E1E3-deleted recombinant human adenovirus serotype 5 reduced human telomerase reverse transcriptase (hTERT) mRNA levels in hepatoma cell lines. We defined the mechanisms by which the recombinant adenovirus vector reduces hTERT mRNA levels as follows: Using the virus-associated RNA I/II (VAI/II) expression construct, we demonstrated that the expression of VAI and VAII RNAs led to an increase in IFN-α2 level, and IFN-α2 induction was responsible for the decrease in hTERT mRNA levels. We showed that the effects of VA RNAs were specific for the replication-incompetent E1E3-deleted adenovirus vector, because wild-type adenovirus affected neither IFN-α2 nor hTERT mRNA levels. Moreover, we demonstrated that adenovirus vector-mediated delivery of the hTERT-targeting anti-cancer reagent could additively reduce the levels of hTERT mRNA that were specifically overexpressed in most of the cancer cells. This study showed that E1E3-deleted adenovirus vector system reduced hTERT mRNA levels through VA RNA-mediated induction of type 1 interferon; hence the recombinant adenovirus itself could have anti-cancer activity. These results indicate that recombinant adenovirus vector could be an effective means to deliver anti-cancer reagents for combating cancerous cells more effectively. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 02/2015; 458(4). DOI:10.1016/j.bbrc.2015.02.039 · 2.28 Impact Factor
Show more

Questions & Answers about this publication

  • Bernardino Isaac Cerda-Cristerna added an answer in Adeno-associated Virus:
    What is the most common virus used in clinical trials in gene therapy?

    I wonder if it is adeno or adeno-associated virus?

    Bernardino Isaac Cerda-Cristerna · Universidad de Veracruz

    "Recent years have seen a decline in the use of retroviral vectors (currently, only 19.7% of trials compared to 22.8% in 2007 and 28% in 2004), presumably as a result of the severe adverse events observed in the SCID trials, and research is well underway towards engineering safer retroviral vectors. Adenoviruses are the most commonly used vector (23.3% of all trials)". From Ginn et al. The paper is free here