Human Gene Transfer Research
- Overview of Gene Transfer Research
- Federal Oversight and Review Requirements
- UCI Oversight and Review Requirements
- Reporting Adverse Events
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 the 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). 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 the NIH Recombinant DNA Advisory Committee (RAC).
Federal Oversight and Review Requirements
Human Gene Transfer Research is defined by federal regulations as, "Any deliberate transfer of recombinant DNA, or DNA or RNA derived from recombinant DNA (technology), into human research participants."
The NIH Office of Biotechnology Activities (OBA) exists because human gene transfer research raises scientific, medical, ethical, and social considerations worthy of special attention and public discussion. Some of these issues arise from the fact that the techniques being used are relatively new and their risks and benefits are not well characterized.
The NIH OBA review process allows for an in-depth examination of the issues associated with this technology in a setting where public input and comment is encouraged. This open discussion has two important benefits:
- It disseminates this information to scientists who can then incorporate new scientific findings and ethical considerations into the design of trials they may be conducting or planning. The efficiency of the research system is improved by allowing scientists to build on a common foundation of new knowledge emanating from this ongoing process of analysis and assessment.
- It creates enhanced public awareness and allows for a public voice in the review of the safety and ethics of gene transfer research. This helps assure the public that scientists are attending to these important matters and sustains confidence in the enterprise.
The Recombinant DNA Advisory Committee (RAC)
The RAC is a panel of up to 21 national experts in various fields various fields of science, medicine, genetics, ethics, and patient perspectives that considers the current state of knowledge and technology regarding recombinant DNA research. A key role of the RAC is to advise the NIH Director and the NIH Office of Biotechnology Activities (OBA), which is the NIH locus of oversight for recombinant DNA research. In this capacity, the RAC recommends changes to the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines), which outline responsible research practices in basic and clinical recombinant DNA research.
Another important RAC function is to review research proposals involving human gene transfer research, or "gene therapy" as it is often called. All human gene transfer trials occurring at or sponsored by institutions receiving NIH funds for recombinant DNA research must be submitted to OBA for review by the RAC.
To learn more about the RAC, please visit the OBA website.
Who is Responsible for the RAC Submission?
See the RAC Submission Flowchart for an overview of the submission process.
- For UCI investigator initiated studies (i.e., the production of vectors for human application is performed by the UCI investigator), the UCI investigator is responsible for the submission of the relevant information on the proposed human gene transfer experiments to NIH Office of Biotechnology Activities (OBA) in accordance with Appendix M of the NIH Guidelines.
- For Sponsor initiated studies (i.e., the production of vectors for human application is not performed by the UCI investigator) the Sponsor must complete the RAC submission process and provide the UCI investigator with the required Appendix M information for the IBC review.
UCI Oversight and Review Requirements
Human Gene Transfer studies must be reviewed by the UCI Institutional Biosafety Committee (IBC) and the UCI Institutional Review Board (IRB). IBC review should precede the IRB review. IBC approval is required before IRB approval may be granted.
IBC Review and Submission
Effective January 1, 2007, Environmental Health & Safety has assumed all administrative support responsibilities for the Recombinant DNA Activities Program and the Institutional Biosafety Committee. All issues related to this program should be addressed to the Campus Biosafety Officer at (949) 824-9888.
More information is available on the EH&S 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. See "How to Submit Protocols to the IRB" for detailed information.
IRB Submission Requirements
Provide the following information with your submission to the IRB:
- UCI IRB application
- 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
- IBC approval letter
- Note: the IBC approval must be granted before IRB approval may be granted.
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. Contact Sheila Hedayati at 949-824-9888 or shedayat@uci.edu, or visit the EH&S Biosafety website for more information.
Notification to NIH-OBA of UCI Approvals
Evidence of UCI approvals should be provided by the UCI investigator to the NIH-OBA unless the the study is sponsor initiated. In the latter case, the UCI investigator should provide this information to the sponsor of the study for submission to NIH-OBA.
No research participant may be enrolled at UCI site until the following documentation has been submitted to NIH-OBA:
- UCI IBC approval letter
- UCI IRB approval letter and (IRB stamped) informed consent document
- Curriculum vitae of the Lead Researcher and any Co-investigators
- NIH grant number(s), if applicable
Reporting Adverse Events for Human Gene Transfer Studies
All adverse events must be submitted to the UCI IRB. See the Adverse Events webpage for detailed information.
The IBC must also review adverse events occurring on human gene transfer studies.
AEs submitted to the IRB should be printed out and submitted to the IBC for full committee review. A memo signed by the Lead Researcher must be provided with the AE submission. The memo should discuss:
- The AE in relation to the gene product and/or the vector.
- How the AE affected the subject, whether the subject was withdrawn from the study, etc.
- 15 copies of the AE and summary memo are required for IBC review.
