Human Gene Transfer
“Human Gene Transfer” or “HGT” is used to describe research involving the transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA, into human subjects. It is also sometimes referred to as “Gene Therapy.” HGT is currently being investigated by researchers at Ohio State in a variety of human diseases to see whether it can treat certain health problems by supplying a missing protein, compensating for a defective gene, providing a therapeutic substance, or activating the subject’s own immune response.
HGT touches on a number of scientific, medical, ethical, and safety issues. The National Institutes of Health (NIH) Office of Biotechnology Activities (OBA), the office charged with oversight of recombinant DNA research, is responsible for publishing and updating the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (“NIH Guidelines”). The NIH Guidelines set forth the guiding principles regarding oversight and provide specific guidance on the conduct of human gene transfer to ensure the safe handling and containment of recombinant DNA. Review of HGT protocols may involve the federal Recombinant DNA Advisory Committee (RAC), which includes experts in a variety of fields including medicine, genetics, and ethics who review proposed human gene transfer research in the context of current technology and scientific understanding of recombinant DNA research.
The NIH Guidelines were recently updated and streamlined such that local oversight bodies (e.g. Institutional Biosafety Committee [IBC] or Institutional Review Board [IRB]) are now responsible for determining whether an HGT protocol submitted for approval would significantly benefit from review by the RAC. RAC review of individual HGT protocols will be requested and performed only in exceptional cases determined by the IBC to meet one or more of the following criteria:
- The protocol uses a new vector, genetic material, or delivery system for first-in-man testing,
- The protocol relies on preclinical safety data obtained using a new preclinical model system of unknown and unconfirmed value, or
- The proposed vector, gene construct, or delivery system is associated with toxicities that are not widely known and that may render it difficult for an oversight body to evaluate the protocol rigorously.
Additionally, HGT protocols may be reviewed by the RAC if the NIH Director determines the research presents significant scientific, societal, or ethical concerns.
At OSU, HGT research must be reviewed and approved locally by the IBC and the IRB. Lastly, all HGT research at Ohio State must undergo a formal institutional review and approval process, which includes coordination of special contract provisions, risk assessments, and College and University administration approvals. For additional information on conducting HGTs at the university, see the institutional policy on Human Gene Transfer along with the Human Gene Transfer Flowchart for an overview of the HGT Institutional Review Process.
The IBC and Office of Research Compliance coordinate the HGT review process at the university, which is briefly described above. The first step is that investigators should register their HGT research with the IBC. For more information, see the Investigator Guidance. For general information on HGT clinical trial research, contact Courtney Mankowski, Research Integrity and Compliance Manager at email@example.com or (614)292-5714.
- NIH Guidelines, Appendix M
- RAC Revisions Fact Sheet
- FAQs about the NIH Review Process for Human Gene Transfer Trials
- FAQs about the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules
- FAQs about the NIH Guidelines Vaccine Exemption
- FAQs about Experiments that are Exempt from the NIH Guidelines