- Overview of Gene Transfer Research
- UCI Oversight and Review Requirements
- Serious Adverse Event Reporting Requirements for Human Gene Transfer Research
Overview of Human Gene Transfer Research
The following explanations are provided to assist investigators in determining whether their proposed research may constitute human gene transfer and, therefore, require additional oversight.
What is DNA?
Deoxyribonucleic acid (DNA) is the building block of life. This molecule encodes different characteristics in all living things. With the exception of identical twins, all individuals have different DNA molecules. In some individuals, the DNA contain mutations that encode aberrant messages. These mutations can cause abnormalities that may result in disease.
What is not Human Gene Transfer Research?
When DNA is manipulated outside of the body but is not integrated into a person's genome, it is an example of recombinant DNA (rDNA) research but is not gene transfer. Likewise, if protein or RNA products of the rDNA are injected into a person, no gene transfer has occurred.*
Experiments involving rDNA require review and approval by the UCI Institutional Biosafety Committee (IBC) or their designee. Institutional Review Board (IRB) review and approval is required if human subjects are involved. Institutional Animal Care and Use Committee (IACUC) review and approval is required if vertebrate animals are used.
*Note: use of retroviral vectors constitutes human gene transfer.
What is Human Gene Transfer (a.k.a. "Gene Therapy")?
Human gene transfer is the process of transferring genetic material (DNA or RNA) into a person. DNA may be transferred as "naked" DNA, encapsulated DNA, or DNA within another organism, such as a virus. Use of retroviral vectors in humans also constitutes human gene transfer when the virus contains enzymes that result in a DNA copy of the RNA genome.
Human gene transfer is experimental and is being studied to see whether it could treat certain health problems by compensating for defective genes, producing a potentially therapeutic substance, or triggering the immune system to fight disease. Human gene transfer may help improve genetic disorders, particularly those conditions that result from inborn errors in a single gene (for example, sickle cell anemia, hemophilia, and cystic fibrosis). It may also hold promise for diseases with more complex origins, like cancer and heart disease. Gene transfer is also being studied as a possible treatment for certain infectious diseases, such as AIDS. This type of experimentation is sometimes called "gene therapy" research.
Scientists are attempting to determine whether human gene transfer can be safe and effective as a treatment for disease. Some experimental gene transfer procedures involve the introduction of DNA into cells, which then are injected into a person with disease. All such human gene transfer research studies require approval by the UCI Institutional Review Board (IRB), the UCI Institutional Biosafety Committee (IBC), and possibly the NIH Recombinant DNA Advisory Committee (RAC).
All human gene transfer protocols subject to the NIH Guidelines must be registered with the NIH and be reviewed and approved by institutional oversight bodies such as the IBCs and IRBs.
UCI Oversight and Review Requirements
Human Gene Transfer studies must be reviewed by the UCI Institutional Biosafety Committee (IBC) or their designee and the UCI Institutional Review Board (IRB). IBC review is concurrent with IRB review of new protocols. IRB approval will be granted upon receipt of the IBC approval letter. If, however, substantive changes to the IRB protocol are required based on IBC determination or RAC review, additional IRB review will be required to confirm that changes meet requirements for IRB approval under 45 CFR 46.111 and 21 CFR 56.111.
IBC Review and Submission
Environmental Health & Safety assumes all administrative support responsibilities for the Recombinant and Synthetic Nucleic Acid Activities Program and the UCI IBC. All issues related to this program should be addressed to the Campus Biosafety Officer at (949) 824-4365.
More information is available on the UCI IBC website.
IRB Review and Submission
Human gene transfer research requires review by the IRB. The IRB protocol submission requirements for human gene transfer studies are the same as with other human research protocols.
IRB Submission Requirements
Provide the following information with your submission to the IRB:
- Informed consent document
- Additional consent elements unique to human gene transfer research should be included in the IRB informed consent document, such as reproductive considerations; long term follow-up (FDA requires 15 years or until death); autopsy to study pathology of disorder/illness; risk of media interest in the study.
- Note: Investigators should review the NIH Guidance on Informed Consent For Gene Transfer Research for useful information about preparing the informed consent document and performing the informed consent process.
- The FDA Investigational New Drug (IND) number
- Sponsor's Master Protocol
Other UCI Reviews
The hospital (UCIMC) also reviews human gene transfer studies to assure adequate facilities are available to perform the study. See the Gene Medicine Advisory Committee website for more information. Note: you must have HSIS Intranet access to view this link.
The campus Biosafety Officer will review the Clinical safety standard operating procedures (SOPs) for the conduct of human gene transfer studies. Visit the EH&S Biosafety website for more information.
Serious Adverse Event (SAE) Reporting Requirements for Human Gene Transfer Research
All unanticipated problems must be submitted to the UCI IRB. The LR must submit SAEs to the UCI Institutional Biosafety Committee (IBC), and any unanticipated problems to the UCI IRB.