? CORE B The main function of Vector Development Core (VDC) B is to develop new lentiviral vectors (LV) and the means for their production in order to facilitate their use in clinical trials proposed in Projects 1, 2, and 3. Core B will achieve this aim by 1) producing small-scale vectors including LV, IDLV, and AAV for preclinical testing; 2) exploring new methodologies for vector manufacturing such as transient transfection in suspension cells and stable cell line production systems; 3) developing next generation producer cell lines from suspension cells growing in serum-free media; 4) developing process for scale-up manufacturing that bridges laboratory research to cGMP production; 5) optimizing protocols for LV transduction of human hematopoietic stem cells (HSCs). As such, Core B provides a critical link between the Projects and cGMP production in Core C by performing developmental studies, by providing the scientific expertise for process transfer, and by providing novel and unique reagents, vectors, and cell lines for these purposes. These research activities in Core B will ultimately integrate into all projects for improved vector manufacturing and cell transduction.

Public Health Relevance

? CORE B Core B is essential to develop lentiviral vectors for clinical gene therapy of sickle cell disease and novel platform using suspension-based vector manufacturing that will increase potency of vectors and reduce manufacturing costs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
2P01HL053749-21A1
Application #
9572183
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Qasba, Pankaj
Project Start
Project End
Budget Start
2018-08-01
Budget End
2019-06-30
Support Year
21
Fiscal Year
2018
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Zhao, Hui Fen; Abraham, Allistair; Kim, Yoon-Sang et al. (2017) Lentiviral Transfer of ?-Globin with Fusion Gene NUP98-HOXA10HD Expands Hematopoietic Stem Cells and Ameliorates Murine ?-Thalassemia. Mol Ther 25:593-605
De Ravin, Suk See; Wu, Xiaolin; Moir, Susan et al. (2016) Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med 8:335ra57
Abraham, Allistair; Kim, Yoon-Sang; Zhao, Huifen et al. (2016) Increased Engraftment of Human Short Term Repopulating Hematopoietic Cells in NOD/SCID/IL2r?null Mice by Lentiviral Expression of NUP98-HOXA10HD. PLoS One 11:e0147059
Wielgosz, Matthew M; Kim, Yoon-Sang; Carney, Gael G et al. (2015) Generation of a lentiviral vector producer cell clone for human Wiskott-Aldrich syndrome gene therapy. Mol Ther Methods Clin Dev 2:14063
Pestina, Tamara I; Hargrove, Phillip W; Zhao, Huifen et al. (2015) Amelioration of murine sickle cell disease by nonablative conditioning and ?-globin gene-corrected bone marrow cells. Mol Ther Methods Clin Dev 2:15045
Zhou, Sheng; Bonner, Melissa A; Wang, Yong-Dong et al. (2015) Quantitative shearing linear amplification polymerase chain reaction: an improved method for quantifying lentiviral vector insertion sites in transplanted hematopoietic cell systems. Hum Gene Ther Methods 26:4-12
Urbinati, Fabrizia; Hargrove, Phillip W; Geiger, Sabine et al. (2015) Potentially therapeutic levels of anti-sickling globin gene expression following lentivirus-mediated gene transfer in sickle cell disease bone marrow CD34+ cells. Exp Hematol 43:346-351
Yu, Hui; Neale, Geoffrey; Zhang, Hui et al. (2014) Downregulation of Prdm16 mRNA is a specific antileukemic mechanism during HOXB4-mediated HSC expansion in vivo. Blood 124:1737-47
Treanor, Louise M; Zhou, Sheng; Janke, Laura et al. (2014) Interleukin-7 receptor mutants initiate early T cell precursor leukemia in murine thymocyte progenitors with multipotent potential. J Exp Med 211:701-13
Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D et al. (2014) Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol 133:335-47

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