The National Institutes of Health (NIH) Office of Science Policy has amended the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) to include work with synthetic nucleic acids, as well as other forms of recombinant nucleic acid research.
The amendments are effective March 2013 and stand to impact research involving most forms of DNA, RNA, or their equivalents.
This webpage provides a summary of the amended NIH Guidelines, instructions for Principal Investigators (PIs) with research impacted by the amendments, and other information pertinent to the transition.
The below amendments should be reviewed by PIs as they may impact ongoing and proposed research with recombinant and/or synthetic nucleic acid molecules.
Compliance with the NIH Guidelines is required for all UW PIs regardless of funding source because the UW as an institution receives NIH funding for recombinant and synthetic nucleic acid research.
PIs needing Institutional Biosafety Committee (IBC) approval and/or registration for their work must submit a BUA application before February 28, 2013.
In the amended NIH Guidelines, recombinant and synthetic DNA molecules are defined as follows:
- Molecules that (a) are constructed by joining nucleic acid molecules and (b) can replicate in a living cell (i.e., recombinant nucleic acids);
- Nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules (i.e., synthetic nucleic acids); or
- Molecules that result from the replication of those described in (i) or (ii) above.
For the amended definition of recombinant and synthetic nucleic acid molecules for human gene transfer, see the EH&S Recombinant or Synthetic DNA/RNA in Human Research Participants webpage.
- In September 2012, the NIH announced several amendments to the NIH Guidelines.
- As a result, PIs working with most forms of DNA, RNA, or their equivalents need to review these changes and, if needed, register their work with the UW Institutional Biosafety Committee (IBC) before February 28, 2013.
- Among other things, these amendments mean that recombinant DNA/RNA molecules generated by synthetic means are now regulated in the same fashion as recombinant DNA/RNA generated by conventional methods. As such, the term "recombinant DNA" has been replaced by the term "recombinant or synthetic nucleic acids". The title of the NIH Guidelines has been amended correspondingly: NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules.
- In general, generation and use of recombinant or synthetic nucleic acids outside of cells, animals and human research participants is exempt. Items (5), (6) and (7) below discuss specific considerations to exemption criteria.
- Although most work with recombinant or synthetic nucleic acids outside of cells continues to be exempt from the NIH Guidelines, there is a new exception: research with recombinant or synthetic nucleic acid molecules that are "encapsulated into synthetic or natural vehicles (so as to) render them capable of penetrating membranes" now falls under Section III-E of the NIH Guidelines and therefore must be registered with the UW IBC.
- Certain categories of research with recombinant or synthetic nucleic acids are also now exempt even when used inside cells. Specifically, the exemption refers to recombinant or synthetic nucleic acid molecules that are "not designed to replicate". According to the new rules, nucleic acid molecules that are small (≤100 bases), do not contain origins of replication or promoters, are not designed to integrate into the host cell genome and do not produce toxins are exempt.
- Certain categories of research remain exempt from the NIH Guidelines when they involve research with synthetic nucleic acids that encode non-recombinant segments from organisms that exist in nature. However, the new rules restrict this exemption to organisms that "exist contemporaneously in nature" (that is, currently exist in nature - the exemption does not apply to extinct organisms or viruses). Although exempt from the NIH Guidelines, if such research involves pathogenic or other non-exempt agents it must still be registered with the UW IBC.
- The new rules now treat chemically modified recombinant or synthetic nucleic acids the same as conventional nucleic acids. All versions of chemically modified nucleic acid molecules that are able to "base pair with naturally occurring nucleic acid molecules" are subject to the NIH Guidelines.
- The definition of human gene transfer (Section III-C of the NIH Guidelines) has been amended. The amended definition exempts studies involving recombinant or synthetic nucleic acid molecules as defined in item (6) above from review by the Recombinant DNA Advisory Committee (RAC). Regardless of exemption, all studies involving administration of synthetic or recombinant nucleic acids, or materials derived from synthetic or recombinant nucleic acids, to human research participants require review by the UW IBC. See the EH&S Recombinant or Synthetic DNA/RNA in Human Research Participants webpage for the amended definition of human gene transfer and for more information.
- The criteria used to define when research with certain drug-resistance genes in pathogenic agents must be reviewed by the RAC (Section III-A of the NIH Guidelines) have been broadened. See the amended NIH Guidelines for detailed information.
- The criteria that should be used by PIs and IBCs in carrying out their risk assessments have been broadened. See the amended NIH Guidelines for detailed information.
- Although many forms of research with recombinant or synthetic nucleic acids remain exempt from the NIH Guidelines, the new rules reiterate that such molecules, by their nature, constitute a biohazard and must be handled and disposed of in an appropriate manner.
PIs with research covered by the amended NIH Guidelines must register their work by submitting a Biological Use Authorization (BUA) application before February 28, 2013.
PIs with current BUAs should submit a Request for Change to BUA.
PIs without current BUAs must submit a full BUA Application.
For more information about BUAs and the IBC approval process see the EH&S BUA webpage.
EH&S is working with the Office of Animal Welfare and Human Subjects Division for the coordinated review of animal and clinical research protocols impacted by the amended NIH Guidelines.
If you have questions related to your research protocol, contact an EH&S biosafety officer at firstname.lastname@example.org or 206.221.7770.
Two information sessions led by the Chair of the Institutional Biosafety Committee have been scheduled to aid in the transition.
Dates, times and locations are below.
PIs with questions and concerns are encouraged to attend.
The presentation slides are available here for your reference.
- January 9, 2013, 2-3PM, Molecular Engineering, 3rd floor conference room
- January 11, 2013, 1-2PM, Magnuson Health Sciences, T-639
Please contact an EH&S biosafety officer at email@example.com or 206.221.7770 with questions.