Title

Stability and compatibility of recombinant adeno-associated virus under conditions commonly encountered in human gene therapy trials

Student Author(s)

Alisha M. Gruntman

Academic Program

Interdisciplinary Graduate Program

UMMS Affiliation

Gene Therapy Center; Viral Vector Core; Department of Microbiology and Physiologic Systems; Department of Pediatrics, Division of Pulmonary and Allergy

Publication Date

2015-04-01

Document Type

Article

Disciplines

Genetics and Genomics | Therapeutics

Abstract

Recombinant adeno-associated virus (rAAV) vectors are rapidly becoming the first choice for human gene therapy studies, as clinical efficacy has been demonstrated in several human trials and proof-of-concept data have been demonstrated for correction of many others. When moving into human use under the auspices of an FDA Investigational New Drug (IND) application, it is necessary to demonstrate the stability of vector material under various conditions of storage, dilution, and administration when used in humans. Limited data are currently available in the literature regarding vector compatibility and stability, leading most IND sponsors to repeat all necessary studies. The current study addresses this issue with an rAAV vector (rAAV1-CB-chAATmyc) containing AAV2-inverted terminal repeat sequences packaged into an AAV1 capsid. Aliquots of vector were exposed to a variety of temperatures, diluents, container constituents, and other environmental conditions, and its functional biological activity (after these various treatments) was assessed by measuring transgene expression after intramuscular injection in mice. rAAV was found to be remarkably stable at temperatures ranging from 4 degrees C to 55 degrees C (with only partial loss of potency after 20 min at 70 degrees C), at pH ranging from 5.5 to 8.5, after contact with mouse or human serum (with or without complement depletion) or with gadolinium and after contact with glass, polystyrene, polyethylene, polypropylene, and stainless steel. The only exposure resulting in near-total loss of vector activity (10,000-fold loss) was UV exposure for 10 min. The stability of rAAV1 preparations bodes well for future dissemination of this therapeutic modality.

DOI of Published Version

10.1089/hgtb.2015.040

Source

Hum Gene Ther Methods. 2015 Apr;26(2):71-6. doi: 10.1089/hgtb.2015.040. Link to article on publisher's site

Journal/Book/Conference Title

Human gene therapy methods

Related Resources

Link to Article in PubMed

PubMed ID

25819833

Link to Full Text

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