| | Principal Investigators
| Maribeth V.
Eiden, Ph.D. |
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Dr.
Eiden is Chief of the Section on Molecular Virology
in the NIMH Intramural Research Program (IRP). She received
her undergraduate degree in microbiology at the University
of Maryland, her doctoral degree in genetics at George
Washington University, and joined the Laboratory of
Cell Biology (now the Laboratory of Cellular and Molecular
Regulation) in 1986.
Dr. Eiden serves on the review board of Journal of Virology,
is chairman of the NIH Intramural Biosafety Committee
and is as a member of NIAID Virology Study Section. |
| Research Interests |
Discovery of the genetic bases of central nervous system (CNS) disorders, development of corresponding animal models, and continued advances in vector-mediated gene delivery have all increased the potential for gene therapies to ameliorate human CNS disease. Viral vector-mediated gene therapy is a reiterative process requiring continual feedback from clinical trial results to ensure the proper direction of translational studies. Modifications to the design of retroviral vectors and delivery modalities based on this feedback are a path towards arresting the progression or relieving the symptoms of human diseases of the CNS.
The goal of the Section on Directed Gene Transfer (SDGT) is to develop and optimize viral vectors based on the knowledge in the areas of fundamental, translational, and applied retrovirology achieved through our progress studying Gibbon Ape Leukemia Virus (GALV) and GALV-related viruses. Retroviral vectors have substantially improved over the last decade and have evolved from the originally employed vectors containing exclusively Murine Leukemia Virus (MLV) components. The PG13 cell line produces vectors, with GALV envelope proteins, that can be adapted to package various therapeutic genes. This GALV-enveloped vector producer cell line is based on our initial research on the structural components of the parent virus. The development of GALV vectors, the first primate retrovirus-based vector platform, paved the way for strategic basic collaborations between academic and biotech systems partners who further developed the vector into a clinical product. Since their development, GALV vectors been employed to successfully treat a number of inherited diseases. Feedback from clinical trials using GALV vectors has allowed us to make adjustments to GALV vector design. Such adjustments are based not only on hypothesis-driven experiments resulting in successful outcomes, but also on failures of delivery, expression, efficacy or safety that provide a rationale for improving vector properties and features. The latter are frequently not published and tend to be part of the repository of experiences found in a lab. Harvesting translational value from even unsuccessful outcomes in vector development research has been an important component of our extended commitment to overcome the shortcomings of therapeutic retroviral vectors.
Our long-range goal is to design and produce gammaretroviral and lentiviral vectors that express genetic material in an appropriate manner in the human CNS after assessing the vector’s biosafety and effectiveness in cell culture and in animal models. Our laboratory has established itself as uniquely capable of identifying the key factors controlling efficient retroviral mediated entry and gene delivery. The current aims of the SDGT are to determine the viral and cellular factors governing ??retroviral entry into mammalian cells of the CNS, and their long-term maintenance as genetic elements.
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| Representative Selected Recent Publications: |
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Wenqin Xu, Jill L. Russ and Maribeth.V. Eiden: Evaluation of residual promoter activity in gammaretroviral self-inactivating vectors.. Molecular Therapy , 2012 January:20 (1): 84-89
PMID 22008914. <view>
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Andrew C. Emery, Maribeth V. Eiden and Lee E. Eiden: A new site and mechanism of action for the widely used adenylate cyclase Inhibitor SQ22,536 Molecular Pharmacology, 2012 Oct 10 PMID: 23053667
. <view>
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Xiuhuai Liu, Jill L. Russ, Lee E. Eiden and Maribeth V. Eiden: The host range of gammaretroviruses and gammaretroviral vectors includes post-mitotic and neural cells. PLoS One , 2011 Mar: 28:6(3)
PMID: 21464894. <view>
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Meihong Liu and Maribeth V. Eiden: A mutant retroviral receptor restricts virus superinfection interference and productive infection. Retrovirology, 2012 Jun 12;9:51. doi: 10.1186/1742-4690-9-51.
PMID 22691439
. <view>
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Wenqin Xu and Maribeth V. Eiden: Primate gammaretroviruses require an ancillary factor not required for murine gammaretroviruses to infect BHK cells. Journal of Virology, Vol. 85:3498-3506, 2011. PMID 21270153. <view>
|
Address:
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Chief, Section on Directed Gene Delivery
National Institute of Mental Health
Laboratory of Cellular & Molecular Regulation
Building 49, Room 5A32
49 Convent Dr., MSC 4483
Bethesda, MD 20892 |
| Phone: |
(301) 402-1641
(office), (301) 435-7523 (laboratory) |
| Email
Dr. Eiden |
| Fax: |
301-402-1748 |
| Lab Web Site: |
http://intramural.nimh.nih.gov/lcmr/ |
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