Foamy viruses (FVs) are integrating retroviruses with many properties that distinguish them from gammaretroviruses or lentiviruses;one important characteristic for gene therapy applications is that FV are nonpathogenic. FV vectors have improved from early replication competent vectors to advanced vectors that do not contain detectable replication competent retroviruses. Importantly, with the exception of persons exposed to primates, FV vectors do not infect humans, and uninfected humans do not have antibodies to FV vectors, which makes them also ideal vectors for in vivo delivery. FV vectors can transduce pluripotent murine and human repopulating cells, and for human CD34+ repopulating cells this was unequivocally demonstrated by sequencing and identifying identical FV vector integration sites in repopulating myeloid and lymphoid cells. Significant silencing of vector transgenes in either murine or human repopulating cells was not observed in these studies. Importantly, FV vectors efficiently transduce long-term repopulating hematopoietic stem cells (HSC) in the canine large animal model with high levels of marked granulocytes and lymphocytes. Thus, FV vectors are potentially the best currently available vector system for the correction of genetic diseases like SCID-X1. Dr. Kiem has extensive experience with the development and generation of new vector systems. He has studied gammaretrovirus, lentivirus and FV vectors in large animal models and is, therefore, very familiar with large-scale vector production and experiments conducted in large animals like dogs. Dr. Kiem has also significant expertise in clinical vector production and gene therapy studies. The FHCRC has a fully established cGMP facility for clinical grade vector production. Core B will provide the following resources to all 3 Projects within this application: 1)Provision of FV Vectors, 2) Optimization of FV vector production and 3) Clinical GMP-grade FV vector production.

Public Health Relevance

Foamy virus vectors offer a unique combination of properties that render this gene delivery system a superior choice for retrovirus gene therapy and for therapeutic gene corrections with inherited immunological diseases such as SCID-X1.

National Institute of Health (NIH)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Seattle Children's Hospital
United States
Zip Code
Everson, Elizabeth M; Trobridge, Grant D (2016) Retroviral vector interactions with hematopoietic cells. Curr Opin Virol 21:41-46
Bii, Victor M; Trobridge, Grant D (2016) Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors. Cancers (Basel) 8:
Everson, Elizabeth M; Olzsko, Miles E; Leap, David J et al. (2016) A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance. Mol Ther Methods Clin Dev 3:16048
Hocum, Jonah D; Linde, Ian; Rae, Dustin T et al. (2016) Retargeted Foamy Virus Vectors Integrate Less Frequently Near Proto-oncogenes. Sci Rep 6:36610
Adair, Jennifer E; Waters, Timothy; Haworth, Kevin G et al. (2016) Semi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy. Nat Commun 7:13173
Humbert, Olivier; Gisch, Don W; Wohlfahrt, Martin E et al. (2016) Development of Third-generation Cocal Envelope Producer Cell Lines for Robust Lentiviral Gene Transfer into Hematopoietic Stem Cells and T-cells. Mol Ther 24:1237-46
Browning, Diana L; Collins, Casey P; Hocum, Jonah D et al. (2016) Insulated Foamy Viral Vectors. Hum Gene Ther 27:255-66
Rae, Dustin T; Collins, Casey P; Hocum, Jonah D et al. (2015) Modified Genomic Sequencing PCR Using the MiSeq Platform to Identify Retroviral Integration Sites. Hum Gene Ther Methods 26:221-7
Felsburg, Peter J; De Ravin, Suk See; Malech, Harry L et al. (2015) Gene therapy studies in a canine model of X-linked severe combined immunodeficiency. Hum Gene Ther Clin Dev 26:50-6
Gori, Jennifer L; Butler, Jason M; Chan, Yan-Yi et al. (2015) Vascular niche promotes hematopoietic multipotent progenitor formation from pluripotent stem cells. J Clin Invest 125:1243-54

Showing the most recent 10 out of 35 publications