OBA - Archived News and Events

Help | Sitemap | Contact us

Printer Friendly Page

Home

Recombinant DNA

Genetics, Health, and Society

Dual Use Research

Clinical Research Policy

	About RAC
	News and Events
	RAC Meetings
	Frequently Asked Questions
	Documents of Interest
	GeMCRIS
	NIH Guidelines
	Informed Consent
	IBC Information
	Educational Materials

Archived News and Events - RAC



Past Recombinant DNA News

	OBA Seeking Comment on Proposed Updates to Risk Group Classifications

	The Office of Biotechnology Activities (OBA) is updating Appendix B of the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) by specifying the risk group (RG) classification for several attenuated strains of bacteria and viruses that are frequently used in recombinant DNA research. OBA is also assigning to risk groups several viruses not previously listed in Appendix B.

	The NIH Guidelines provide guidance to investigators and local Institutional Biosafety Committees (IBCs) for setting containment for recombinant DNA research. Section II-A, Risk Assessment, instructs investigators and IBCs to make an initial risk assessment using the RG classification of the agent from Appendix B as a starting point for the risk assessment. For the most part, the organisms listed in Appendix B are wild-type, non-attenuated strains and a distinction is not made between the RG classification for the wild-type organism and a corresponding attenuated strain.

	A few attenuated strains of organisms are classified in Appendix B at a lower RG than that of the parental organism. However, there are a number of additional, well-established attenuated strains employed in research subject to the NIH Guidelines that are not specifically listed and thus by default are included in the same RG as the wild-type organism. After extensive consultation with outside experts, including the NIH Recombinant DNA Advisory Committee, OBA has conducted an evaluation of certain attenuated strains, focusing on those for which a risk assessment has been undertaken and containment recommendations have been determined in the Centers for Disease Control and Prevention (CDC)/NIH publication Biosafety in Microbiological and Biomedical Laboratories (BMBL) (5th edition). Specifying the risk groups for these attenuated strains in Appendix B of the NIH Guidelines will lead to more uniform containment recommendations that are commensurate with the biosafety risk. In addition, OBA has identified several RG3 viruses that are not currently specified in Appendix B or are currently specified as a member of a family of viruses otherwise classified as RG2. Therefore, Appendix B is being updated to address these viruses as well.

	Details of the changes, including the specific organisms in question, can be found in a July 25, 2011, Federal Register notice. The public is encouraged to submit written comments on this minor action by September 9, 2011. Comments may be submitted to OBA by email or by regular mail to NIH Office of Biotechnology Activities (Attn: Appendix B Comments), 6705 Rockledge Drive, Suite 750, Bethesda, MD 20892.

	(Posted July 26, 2011)

	NIH Proposes to Exempt Certain Low-Risk Transgenic Rodent Breeding Experiments from the NIH Guidelines for Research Involving Recombinant DNA Molecules

	Based on suggestions from the scientific community, as well as input from the Recombinant DNA Advisory Committee, the NIH Office of Biotechnology Activities (OBA) has published a proposal to revise the NIH Guidelines to exempt the breeding of well-characterized transgenic rodents that can be maintained under Biosafety Level (BL) 1 conditions. This exemption would not apply, however, to the breeding of rodents that have a gene encoding more than fifty percent of an exogenous eukaryotic virus or those transgenic rodents in which the transgene is under the control of a gammaretroviral promoter.

	The full version of the proposal may be found in the July 20, 2010 Volume 75, number 138 Federal Register

	Comments on the proposal may be submitted to OBA by email at oba@od.nih.gov, by fax to 301-496-9839, or by the postal service at: 6705 Rockledge Drive, Suite 750, Bethesda, Maryland 20892-7985. All comments on the proposed revisions must be submitted by September 1, 2010. All written comments received will be available for public inspection weekdays between the hours of 8:30 a.m. and 5:00 p.m. in the NIH OBA office at the address above.

	If you have questions, or require additional information about these proposed revisions, please feel free to contact OBA at 301-496-9838 or oba@od.nih.gov.

	(Posted August 2, 2010)

	Clonal Population of Cells Detected in a Clinical Human Gene Transfer Trial Using Lentiviral Vector

	The National Institutes of Health Office of Biotechnology Activities (OBA) has been informed that a "relative clonal dominance" was detected during follow-up of a subject who is participating in a French human gene transfer trial being conducted for individuals with β-Thalassemia Major and Sickle Cell Anemia. The clinical trial, sponsored by Genetix France, used hematopoietic stem cells transduced by a self inactivating (SIN) HIV-1 lentiviral vector containing the gene for β-globin under the control of the β-globin promoter. The subject received the gene modified cells in June 2007.

	This clonal dominance appears to result from the integration of the vector in the gene encoding for the HMGA2 protein, which is associated with both benign and malignant tumors. The clone however has been stable for five months and the subject remains in good health. In fact, although the subject required almost monthly blood transfusions during the 11 months prior to the gene transfer intervention, the subject has not since required a blood transfusion.

	The investigators involved in this trial will be performing further studies to evaluate the consequences of this integration and its capacity to proliferate. Until these studies are completed and another review is performed by the French Medicine Agency, AFSSAPS, no other subjects in this study will receive the gene modified cells.

	OBA has sent a memorandum to inform OBA-registered investigators who are using or propose to use lentiviral or retroviral vectors in hematopoietic or other stem cells. OBA is currently seeking additional information regarding this event such as the specifics of the vector used, the dose of the cells, transduction conditions, and the clinical course of the first subject treated in this trial. OBA will organize a discussion at a meeting of the NIH Recombinant DNA Advisory Committee (RAC) when this information is available.

	(Posted May 28, 2010)

	NIH Recombinant DNA Advisory Committee to Discuss a Request to Certify Kluyveromyces lactis as a New Host-Vector System

	At its December 7-8, 2010 meeting, the NIH Recombinant DNA Advisory Committee (RAC) discussed a proposal to certify Kluyveromyces lactis as a new host-vector system under the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines). A new host-vector system may be certified only after review by the NIH RAC and specific approval by the NIH Director as a Major Action. The second part of this proposal is to exempt from the NIH Guidelines certain types of research when performed in K. lactis, if K. lactis and its affiliated plasmids meet the requirements for certification as a host-vector system. Research performed in certain certified host-vector systems is exempt from the NIH Guidelines only after a determination has been made by the NIH Director that this research does not pose a significant risk to human health or the environment.

	In order to certify a new host-vector system, data specified in Appendix I-II-B of the NIH Guidelines must be submitted for review. Specifically, this application will be considered under Appendix I-II-B-1 (Host-Vector 1 Systems Other than Escherichia coli K-12) of the NIH Guidelines. Data to be considered include:


	1.the strain's natural habitat and growth requirements; its physiological properties, particularly those related to its reproduction, survival, and the mechanisms by which it exchanges genetic information; the range of organisms with which this organism normally exchanges genetic information and the type of information that is exchanged; and any relevant information about its pathogenicity or toxicity; 2.a description of the history of the particular strains and vectors to be used, including data on any mutations which render this organism less able to survive or transmit genetic information; and 3.a general description of the range of experiments contemplated with emphasis on the need for developing such a Host-Vector 1 system.




	The public is encouraged to comment in writing and/or in person at the December RAC meeting.

	Information regarding this request, including the Federal Register notice is included below. For additional information please contact Dr. Eugene Rosenthal at 301-496-9838 or by email at rosenthg@od.nih.gov.

	Request for Certification of a New Host Vector System from New England BioLabs (NEB) Background information submitted by NEB: Kluyveromyces lactis Host-vector System Federal Register Notice Supporting articles: Heterologous protein production in the yeast Kluyveromyces lactis On the Safety of Kluyveromyces lactis -a review

	(posted November 17, 2010)

	The NIH RAC and CliniGene Co-host a Scientific Symposium on "Retroviral and Lentiviral Vectors for Long-Term Gene Correction: Clinical Challenges in Vector and Trial Design"

	In past safety symposia, the RAC reviewed clinical and molecular data concerning leukemias caused by insertional mutagenesis at or near oncogenes in two trials for X-linked Severe Combined Immunodeficiency Disease (X-SCID) involving transduction of CD34+ hematopoetic stem cells by retroviral vectors. Since these discussions, investigators have reported advances in the field, including clinical benefits in trials studying other clinical indications (e.g., adenosine deaminase deficient-SCID, adrenoleukodystrophy). In addition, research has focused on alternative vectors, either lentiviral vectors or modified retroviral vectors designed to decrease the risk of enhancer-mediated insertional mutagenesis.

	Given these developments, as well as recent reports of myelodysplasia in a trial for chronic granulomatous disease and the finding of a relative clonal population of cells in a trial for thalassemia, the NIH Recombinant DNA Advisory Committee (RAC) and the European Network for the Advancement of Clinical Gene Transfer and Therapy (CliniGene) are holding this symposium to review:



		Developments in retrovirus and lentivirus integration and insertional mutagenesis research, including non-enhancer mediated mechanisms of insertional mutagenesis;

		Modifications to retroviral and lentiviral vectors to enhance their safety;

		Research on in vitro and animal models to evaluate the safety of human gene transfer; and

		Clinical and ethical considerations for review of human gene transfer research involving novel retroviral and lentiviral vectors.


	The symposium was held December 9-10, 2010 at the Bethesda Marriott, 5151 Pooks Hill Road, Bethesda, MD. A draft agenda is available on the meetings page of the OBA website. This meeting is open to the public and free of charge. Participants are not required to preregister. Seating is available on a first come basis.

	For more information, please contact OBA, by email or by telephone at 301-496-9838.

	(Posted October 20, 2010)

	OBA Partnered with FDA in Planning Upcoming "Workshop on Cell and Gene Therapy Clinical Trials in Pediatric Populations"

	OBA collaborated with the FDA in the planning of a one-day workshop to facilitate an exchange of information about best practices in conducting cell and gene therapy clinical trials in pediatric populations. The purpose of the workshop was to gather information from Institutional Review Boards (IRBs), gene and cellular therapy clinical researchers, and other stakeholders regarding best practices related to cell and gene therapy clinical trials in pediatric populations, as well as challenges and considerations in the review of these clinical trials.

	The workshop included panel discussions regarding best practices related to cell and gene therapy clinical trials in pediatric populations including those related to:



		Evaluating novel therapeutic products prior to initiating pediatric clinical studies;

		Identifying and minimizing risks associated with the administration of cell and gene therapy products in pediatric populations;

		Obtaining informed consent and assent; and

		Conducting continuing review of cell and gene therapy products in pediatric populations.


	Agenda and Videocast

	(posted October 26, 2010)

	Conference - Sham Neurosurgical Procedures in Clinical Trials for Neurodegenerative Diseases: Scientific and Ethical Considerations Hyatt Regency Bethesda Hotel, June 30 - July 1, 2010

	(Posted May 24, 2010)

	NIH Proposes Revisions to Section III-E-1 of the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines)

	Proposal

	(Posted June 15, 2009)

	NIH Extends Public Comment Period for the Proposed Revisions to the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines).

	The NIH has extended the public comment period regarding the proposed revisions to the NIH Guidelines . Comments may be submitted to OBA via email at oba@od.nih.gov or mailed to: 6705 Rockledge Drive, Suite 750, Bethesda, Maryland 20892. All comments regarding the proposed revisions must be submitted by June 1, 2009.

	The proposed revisions to the NIH Guidelines include:

		Broadening the scope of the NIH Guidelines, which currently cover laboratory and clinical research involving DNA molecules created via recombinant techniques (i.e., joining of DNA molecules). NIH proposes to encompass nucleic acids that are synthesized chemically or by other means without the use of recombinant technology.

		Revising the criteria for determining when introduction of a drug resistance trait into a microorganism must be reviewed and approved by the NIH Director. NIH proposes to remove the current language regarding a microorganism's ability to acquire the trait naturally, since this criterion may not be determinative of the safety and public health implications of the research. As proposed, this portion of the NIH Guidelines would state, "the deliberate transfer of a drug resistance trait to microorganisms, if such acquisition could compromise the ability to treat or manage disease caused by that microorganism in human and veterinary medicine, or agriculture." The proposed amendment also contains additional language requiring consideration of the utility of the drug in certain subpopulations.

		Changing the level of review for recombinant or synthetic experiments involving more than half but less than two-thirds of the genome of certain viruses in tissue culture, as described in Section III-E-1 of the NIH Guidelines.

	The full version of the proposed changes may be found in the March 4, 2009 Federal Register, Volume 74, Number 41.

	If you have questions or require additional information about these proposed revisions, please feel free to contact OBA at 301-496-9838 or oba@od.nih.gov

	(Posted May 21, 2009)

	NIH Proposes Revisions to the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines)

	For the purposes of clarification and in acknowledgement of the rapidly developing field of synthetic biology, the NIH is proposing a number of amendments to the current NIH Guidelines.

	The proposed revisions to the NIH Guidelines include:

		Broadening the scope of the NIH Guidelines, which currently cover laboratory and clinical research involving DNA molecules created via recombinant techniques (i.e., joining of DNA molecules). NIH proposes to encompass nucleic acids that are synthesized chemically or by other means without the use of recombinant technology.

		Revising the criteria for determining when introduction of a drug resistance trait into a microorganism must be reviewed and approved by the NIH Director. NIH proposes to remove the current language regarding a microorganism's ability to acquire the trait naturally, since this criterion may not be determinative of the safety and public health implications of the research. As proposed, this portion of the NIH Guidelines would state, "the deliberate transfer of a drug resistance trait to microorganisms, if such acquisition could compromise the ability to treat or manage disease caused by that microorganism in human and veterinary medicine, or agriculture." The proposed amendment also contains additional language requiring consideration of the utility of the drug in certain subpopulations.

		Changing the level of review for recombinant or synthetic experiments involving more than half but less than two-thirds of the genome of certain viruses in tissue culture, as described in Section III-E-1 of the NIH Guidelines.

	The full version of the proposed changes may be found in the March 4, 2009 Federal Register, Volume 74, Number 41.

	The public is encouraged to submit comments on the proposed revisions. Comments may be submitted to OBA via email at oba@od.nih.gov or mailed to: 6705 Rockledge Drive, Suite 750, Bethesda, Maryland 20892. All comments on the proposed revisions must be submitted by May 4, 2009.

	If you have questions or require additional information about these proposed revisions, please feel free to contact OBA at 301-496-9838 or oba@od.nih.gov

	(Posted March 26, 2009)

	OBA Posts Frequently Asked Questions about Research Constituting a "Major Action"

	Under Section III-A of the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines), experiments involving the transfer of a drug resistance trait are considered "Major Actions" if the acquisition of the trait could potentially compromise the use of the drug in question to control disease agents in humans, veterinary medicine, or agriculture. Notice of such experiments must be published in the Federal Register. In order to proceed, the experiments must be reviewed by the RAC and specifically approved by the NIH Director. If the NIH approves the experiment, the agency will specify appropriate biosafety containment.

	OBA frequently receives questions about this provision of the NIH Guidelines, and has thus prepared a set of answers, now available on its Web site, to respond to the most frequently asked questions (FAQs). The aim of the FAQs is to provide readily accessible information on the matters most commonly in need of clarification. Institutional staff and investigators may also contact OBA directly by email or telephone with any additional questions they may have. These questions may be directed to Gene Rosenthal, Ph.D., Biotechnology Program Advisor, NIH OBA, at 301-496-9838 or rosenthg@od.nih.gov. Written queries may also be sent to oba@od.nih.gov.

	(Posted March 21, 2008)

	Major Action Approved by the NIH Director

	After a review of public comments and pursuant to the open deliberations of the NIH Recombinant DNA Advisory Committee ( RAC ), the NIH Director has approved two specific research proposals involving the deliberate transfer of a drug resistance trait to a microorganism. NIH approval was required, because these experiments were considered �Major Actions� under Section III-A of the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines). Major Actions include experiments involving the transfer of a drug resistance trait, the acquisition of which could potentially compromise the use of the drug in question to control disease agents in humans, veterinary medicine, or agriculture. The NIH Director�s approval allows Dr. Dan Rockey and Dr. Walter Stamm (at Oregon State University and the University of Washington , respectively) to transfer from Chlamydia suis (a swine pathogen) a gene encoding tetracycline resistance into C. trachomatis (a human pathogen). This approval is specific to Drs. Rockey and Stamm and the particular research proposals in question, which may proceed only under the conditions outlined in NIH�s approval, as published in the October 31 Federal Register. Other investigators intending to transfer tetracycline resistance to Chlamydia or to engage in other types of experiments fitting the characteristics of those described in Section III-A-1-a of the NIH Guidelines, must submit their proposals to NIH OBA for review and approval before these experiments can be initiated.

	(Posted November 1, 2007)

	NIH Recombinant DNA Advisory Committee to Discuss Proposals to Transfer Chloramphenicol Resistance to Rickettsia typhi and Rickettsia conorii

	At its September 17-19, 2007 meeting, the NIH Recombinant DNA Advisory Committee (RAC) will be discussing proposed experiments to transfer chloramphenicol resistance to Rickettsia typhi and Rickettsia conorii. Initiation of these experiments would constitute a Major Action under the NIH Guidelines for Research Involving Recombinant DNA Molecules because they involve the transfer of a drug resistance trait to microorganisms, where the acquisition of that trait could possibly compromise the use of the drug to control disease caused by that microorganism in humans, veterinary medicine, or agriculture. Notice of such experiments must be published in the Federal Register. In order to proceed, the experiments must be reviewed by the RAC and specifically approved by the NIH Director. Appropriate biosafety containment will be specified if the proposals are approved by the NIH. A notice has been published in the Federal Register regarding these experiments, proposed by Dr. David Walker, University of Texas Medical Branch, Galveston, and Dr. Abdu Azad, University of Maryland at Baltimore (copies of each proposal may be downloaded by clicking on the name of the respective investigator). The public is encouraged to comment in writing and/or in person at the September RAC meeting. Written comments can be sent to OBA's email inbox or to Dr. Eugene Rosenthal, Biotechnology Program Advisor, 6705 Rockledge Drive, Suite 750, Bethesda, Maryland 20892-7985. Written comments received by September 6, 2007 will be reproduced and distributed at the September RAC meeting.

	(Posted July 25, 2007)
Top of Page

Disclaimer | Privacy Policy | FOIA | Accessibility | Directions to OBA


	Department of Health and Human Services			National Institutes of Health			Office of Science Policy