• Assistance with protocol development including participation of the Lovelace Quality Assurance Unit
• Conduct studies under FDA Good Laboratory Guidelines
• Facilitate Pre-IND meeting with the Food and Drug Administration
• Preparation of final study report

Lovelace has consulting statisticians and in house personnel that can assist with

• Experimental design
• Data analysis for Final Reports
• Calculation of pharmacokinetic parameters

• Rodents (mice, rats, guinea pigs, hamsters)
• Rabbits
• Ferrets
• Beagle dogs
• Non-human primates (cynomolgus, rhesus, and baboon)
• Specific animal models can be purchased or developed as needed

• Toxicology staff competent to deliver gene therapy product (viral vectors and cells transduced in vitro)
• Veterinary staff capable of portal vein product delivery
• In house and collaborating veterinary staff for intracardiac product delivery
• Inhalation laboratory for delivery of products directly to the respiratory tract

• Real time PCR for analysis of viral vector load
• Western blot
• Cytokine analysis (ELISA and Luminex)
• In situ hybridization
• Immunohistochemistry

• Necropsy facilities for large and small animals – experience collecting tissue for subsequent
  gene analysis
• In House histopathology laboratory – traditional and “special stain” capabilities
• Immunohistochemical method development capabilities
• Board certified pathologists

• In house capabilities for hematology, serum chemistry, and coagulation times
  (see tables below)
• Special analyses can be developed and validated as needed
• Historical data base for rodents, dogs and non-human primates

Hematology Parameters

For all types of RSAs

• 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).
• The submitting investigator must be registered and approved as described under
  “Who Can 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 Pharmacology/Toxicology Studies

• The applicant must provide documentation of a pre-IND FDA meeting/review and FDA-specified pharmacology/toxicology testing recommendations.
• A brief description of the anticipated gene therapy clinical trial must be provided by the applicant.

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 adequately test the gene vector product, the applicant investigator will be asked to provide such information as:

• background data on vector construct
  (plasmid map including restriction sites; packaging cell lines, serotype,etc)
• sequencing data of vector expression cassette
• method of assessing gene transfer and efficacy
• animal model requirements; dosing and schedule

Lovelace Biomedical and Environmental Research Institute is a subsidiary of the Lovelace Respiratory Research Institute.  The Institute has a long history of conducting toxicology studies on a wide spectrum of agents (including inhaled gene products) in a variety of animal species.  Further, the Institute’s expertise in conducting pre-clinical toxicology and pharmacology studies under FDA Good Laboratory Practice Guidelines (21CFR Part 58) makes it uniquely suited to serve as the Pharmacology/Toxicology Core of the NHLBI Gene Therapy Resources Program.