Abstract

The manufacture of clinical grade gene transfer vectors requires the development of efficient, large scale methods that are appropriate for the generation of safe materials to be used in human study subjects. This work involves both laboratory expertise and regulatory oversight of the safety of the products made in the Human Gene Therapy Applications Laboratory (HGTAL).
Specific Aim 1 : The HGTAL will work collaboratively with the AAV preclinical vector development core, Directed by Dr. Xiao Xiao, to translate laboratory AAV production techniques into a scalable and controlled manufacturing process that can be used to produce clinical grade AAV in years 2 and 3 to support the proposed clinical trial that is projected to start in year 3.
Specific Aim 2 : The HGTAL will manufacture and certify a lot of recombinant AAV for the support of a phase 1 dose determination study. This material will also be certified and characterized according to CBER guidelines and will be used supporting toxicology studies.
Specific Aim 3 : The HGTAL will refine and improve upon its AAV vector manufacturing capabilities and will produce at least two subsequent lots of recombinant AAV vector to support a phase II efficacy study. A determination of the size of the lots needed to be produced will be finalized based upon the highest dose which can be administered to patients, as determined in the phase 1 dose escalation study.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54AR050733-01
Application #
6825355
Study Section
Special Emphasis Panel (ZNS1)
Project Start
2003-09-30
Project End
2008-08-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Type
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Goins, William F; Hall, Bonnie; Cohen, Justus B et al. (2016) Retargeting of herpes simplex virus (HSV) vectors. Curr Opin Virol 21:93-101
Beckman, Sarah A; Sekiya, Naosumi; Chen, William C W et al. (2014) The cardiac regenerative potential of myoblasts remains limited despite improving their survival via antioxidant treatment. CellR4 Repair Replace Regen Reprogram 2:
Rosales, Xiomara Q; Malik, Vinod; Sneh, Amita et al. (2013) Impaired regeneration in LGMD2A supported by increased PAX7-positive satellite cell content and muscle-specific microrna dysregulation. Muscle Nerve 47:731-9
Sekiya, Naosumi; Tobita, Kimimasa; Beckman, Sarah et al. (2013) Muscle-derived stem cell sheets support pump function and prevent cardiac arrhythmias in a model of chronic myocardial infarction. Mol Ther 21:662-9
Zheng, Bo; Li, Guangheng; Chen, William C W et al. (2013) Human myogenic endothelial cells exhibit chondrogenic and osteogenic potentials at the clonal level. J Orthop Res 31:1089-95
Kornegay, Joe N; Bogan, Janet R; Bogan, Daniel J et al. (2012) Canine models of Duchenne muscular dystrophy and their use in therapeutic strategies. Mamm Genome 23:85-108
Cassino, Theresa R; Drowley, Lauren; Okada, Masaho et al. (2012) Mechanical loading of stem cells for improvement of transplantation outcome in a model of acute myocardial infarction: the role of loading history. Tissue Eng Part A 18:1101-8
Okada, Masaho; Payne, Thomas R; Drowley, Lauren et al. (2012) Human skeletal muscle cells with a slow adhesion rate after isolation and an enhanced stress resistance improve function of ischemic hearts. Mol Ther 20:138-45
Mendell, Jerry R; Rodino-Klapac, Louise; Sahenk, Zarife et al. (2012) Gene therapy for muscular dystrophy: lessons learned and path forward. Neurosci Lett 527:90-9
Xiang, Guosheng; Yang, Qing; Wang, Bing et al. (2011) Lentivirus-mediated Wnt11 gene transfer enhances Cardiomyogenic differentiation of skeletal muscle-derived stem cells. Mol Ther 19:790-6

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