For all types of RSAs for laboratory services

• The scientific research in gene therapy that is the subject of the RSA must be consistent with the NHLBI Mission (http://www.nhlbi.nih.gov/about/org/mission.htm) or, if the research addresses a disease area consistent with the mission of another NIH Institute, that Institute must agree to cover the cost of the service.
• The investigator must complete the on-line Registration Form on the GTRP main web page and receive approval by the NHLBI Gene Therapy Group (GTG) allowing the investigator to submit an RSA.
• RSA approval and implementation is contingent upon availability of funds in the GTRP. 
• Services provided through an approved RSA are at no cost to the investigator.
• The various types of RSAs are independent of one another.  An applicant Investigator may submit any type of RSA for a qualified gene therapy research project regardless of past or future utilization of GTRP resources for the project.

In addition, for Clinical-Grade Lentiviral Vector Production

• The applicant must have adequate preclinical data and the requisite regulatory and other oversight reviews for the proposed clinical protocol in which the clinical-grade vector will be used.
• Funding must already be secured and documented for the proposed clinical trial.

A  Request for Service Application (RSA) is the mechanism for applying for GTRP resources. Investigators must register on-line and be approved by the NHLBI Gene Therapy Group in order to access the Request for Service Application.

In order for the laboratory to meet the vector production requirements of the clinical study, the applicant investigator will be asked to provide such information as:

• A comprehensive history of the vector construct, including plasmid map and available sequence data
• Vector production plasmid preferences, including preferred envelope for vector pseudotyping
• Documentation of vector titer and transgene expression in investigators preliminary experiments
• Concentration requirements, final formulation media and volume requirements, and total number of particles required to complete clinical trial and pre-clinical testing
• Information regarding the transgene or clinical protocol that may require specical considerations for production and release testing
• The applicant investigator is encouraged to contact the laboratory for assistance in completing the RSA

The Indiana University Vector Production Facility (IU VPF) is in the Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis. The IU VPF has been generating retroviral vectors for over 10 years and has certified over 30 products for clinical use. It has also generated lentiviral vector for clinical use and developed a series of release testing important for certifying vectors.

The IU VPF moved to a newly constructed cleanroom and certification testing facility that opened in 2009. The facility construction was funded, in part, from a construction grant provided by the NIH National Center for Research Resources. The cleanroom is BL3 capable and has 4 dedicated production rooms. Besides an experienced production team, the laboratory has a dedicated certification testing staff that conduct general (ex. sterility, endotoxin, in vitro assay for adventitious agents) and specialized testing (ex. assays for detection of replication-competent lentivirus, and detection of replication-competent retrovirus) focused on assessing the quality of gene therapy products. The IU VPF also has a dedicated molecular diagnostics laboratory performing DNA based assays aimed at assessing the quality and potency of integrating vectors.