Human Gene Transfer
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules
Section III-C-1. Human gene transfer is the deliberate transfer into human research participants of either:
1. Recombinant nucleic acid molecules, or DNA or RNA derived from recombinant nucleic acid molecules, or
2. Synthetic nucleic acid molecules, or DNA or RNA derived from synthetic nucleic acid molecules, that meet any one of the following criteria:
a. Contain more than 100 nucleotides; or
b. Possess biological properties that enable integration into the genome ( e.g. cis elements involved in integration); or
c. Have the potential to replicate in a cell; or
d. Can be translated or transcribed.
Review Requirements
Human gene transfer proposals must first be submitted to the NIH Office of Biotechnology Activities (OBA) for review-see Appendix M-I-A. Requirements for Protocol Submission. See also, Frequently Asked Questions (FAQs) about the NIH Review Process for Human Gene Transfer Trials (information provided by the NIH OBA).
Once NIH OBA review is complete, the project must be submitted to both OHSU's IBC and IRB for review.
Investigators must submit to the IBC:
- Completed responses to Appendix M-see Appendix M-II. Description of the Proposal Memo from NIH/OBA certifying RAC review is complete, and any additional RAC questions with response
- Protocol and Investigator Brochure
- Consent form (use OHSU Gene Transfer Template); also see Appendix M-III. Informed Consent, and specific requirements for human gene transfer consent forms M-III-B-2 IBC Questionnaire for Human Subjects Studies Drug Preparation Instructions
- There may be additional requirements; please review the Investigational Agents Consisting of Recombinant DNA or Infectious Agents policy.
Project Revisions and Continuing Review Requirements:
Follow IRB instructions as usual. The IBC will review all PRAFs and Continuing Review materials and approve prior to IRB approval.
Additional Requirements for Human Gene Transfer Trials:
Appendix M-I-C-3. Annual Reports The NIH Guidelines require an annual report to be submitted to the NIH OBA. Investigators must submit either a copy of the annual report (submit using the electronic IRB) when available, or, a sponsor memo confirming this report has been submitted.
Appendix M-I-C-4. Safety Reporting Investigators must submit, in accordance with this section, Appendix M-I-C-4-a and Appendix M-I-C-4-b, a written report on: (1) any serious adverse event that is both unexpected and associated with the use of the gene transfer product (i.e., there is reasonable possibility that the event may have been caused by the use of the product; investigators should not await definitive proof of association before reporting such events); and (2) any finding from tests in laboratory animals that suggests a significant risk for human research participants including reports of mutagenicity, teratogenicity, or carcinogenicity. The report must be clearly labeled as a "Safety Report" and must be submitted to the NIH OBA and to the local Institutional Biosafety Committee within the timeframes set forth in Appendix M-I-C-4-b. NOTE: Events described above would likely be submitted through regular IRB Unanticipated Problems reporting and will also be reviewed by the IBC. Any event fitting the descriptions above that do not qualify as an Unanticipated Problem per IRB policy must be separately submitted to the IBC.
Long Term Follow Requirements: FDA Guidance on Observing Subjects for Delayed Adverse Events
