Identification of factors that contribute to recombinant AAV2 particle aggregation and methods to prevent its occurrence during vector purification and formulation

Molecular Therapy

Volumn 12, Issue 1, 2005, Pages 171-178

  Wright, J Fraser ^a,b   Le, Tannie ^a   Prado, Joseph ^a   Bahr Davidson, Jennifer ^a   Smith, Peter H ^a   Zhen, Zhu ^a   Sommer, Jurg M ^a   Pierce, Glenn F ^a   Qu, Guang ^a  

^a Avigen Inc   (United States)

^b CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

Adeno associated virus; Ionic strength; Vector aggregation

Indexed keywords

ARGININE; ASPARTIC ACID; CESIUM CHLORIDE; CITRATE SODIUM; GLUTAMIC ACID; GLYCEROL; GLYCINE; HISTIDINE; IODIXANOL; LYSINE; MAGNESIUM SULFATE; MANNITOL; NUCLEASE; NUCLEIC ACID; PARVOVIRUS VECTOR; POLOXAMER; POLYSORBATE 80; SODIUM CHLORIDE; SODIUM DIHYDROGEN PHOSPHATE; SODIUM SULFATE; SORBITOL; SUCROSE; TREHALOSE;

ADENO ASSOCIATED VIRUS; ARTICLE; DENSITY GRADIENT CENTRIFUGATION; DRUG FORMULATION; DRUG PURIFICATION; FREEZE THAWING; GENOME ANALYSIS; HUMAN; HUMAN CELL; ION EXCHANGE CHROMATOGRAPHY; IONIC STRENGTH; PROTEIN AGGREGATION; SIGNAL TRANSDUCTION; VIRUS GENOME; VIRUS INFECTIVITY;

DEOXYRIBONUCLEASES; DEPENDOVIRUS; GENETIC VECTORS; HUMANS; OSMOLAR CONCENTRATION; SCATTERING, RADIATION; TEMPERATURE;

ADENO-ASSOCIATED VIRUS;

EID: 20844434555     PISSN: 15250016     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ymthe.2005.02.021     Document Type: Article

References (25)

1. D. Grimm and J.A. Kleinschmidt Progress in adeno-associated virus type 2 vector production: Promises and prospects for clinical use Hum. Gene Ther. 10 1999 2445-2450
2. K.A. High AAV-mediated gene transfer for hemophilia Ann. N.Y. Acad. Sci. 953 2001 64-67
3. A. Pfeifer and I.M. Verma Gene therapy: Promises and problems Ann. Rev. Genomics Hum. Genet. 2 2001 177-211
4. K.I. Berns Parvoviridae: The viruses and their replication In B.N. Fields D.M. Knipe P.M. Howley et al. (Eds.), Fields Virology 1996 Lippincott-Raven Philadelphia 2173-2197
5. Q. Xie et al. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy Proc. Natl. Acad. Sci. USA 99 2002 10405-10410
6. M.A. Croyle X. Cheng and J.M. Wilson Development of formulations that enhance physical stability of viral vectors for gene therapy Gene Ther. 8 2001 1281-1290
7. J. Huang et al. Aggregation of AAV vectors, its impact on liver directed gene transfer and development of vector formulations to prevent and dissolve aggregation and enhance gene transfer efficiency Mol. Ther. 1 2000 S286
8. J.F. Wright G. Qu C. Tang and J.M. Sommer Recombinant adeno-associated virus: Formulation challenges and strategies for a gene therapy vector Curr. Opin. Drug Discov. Dev. 6 2003 174-178
9. Q. Xie J. Hare J. Turnigan and M.S. Chapman Large-scale production, purification and crystallization of wild-type adeno-associated virus-2 J. Virol. Methods 122 2004 17-27
10. A. Braun L. Kwee M.A. Labow and J. Alsenz Protein aggregates seem to play a key role among the parameters influencing the antigenicity of interferon alpha (IFN-alpha) in normal and transgenic mice Pharm. Res. 14 1997 1472-1478
11. P. Chenuaud et al. Autoimmune anemia in macaques following erythropoietin gene therapy Blood 103 2004 3303-3304
12. T.R. Flotte Immune responses to recombinant adeno-associated virus vectors: Putting preclinical findings into perspective Hum. Gene Ther. 15 2004 716-717
13. G. Gao et al. Erythropoietin gene therapy leads to autoimmune anemia in macaques Blood 103 2004 3300-3302
14. K.A. High et al. Human immune responses to AAV-2 capsid may limit duration of expression in liver-directed gene transfer in humans with hemophilia B Blood 104 2004 121a
15. Z. Zhen Y. Espinoza T. Bleu J.M. Sommer and J.F. Wright Infectious titer assay for adeno-associated virus vectors with sensitivity sufficient to detect single infectious events Hum. Gene Ther. 15 2004 709-715
16. B. Chen T. Arakawa E. Hsu L.O. Harhi T.J. Tressel and S.L. Chien Strategies to suppress aggregation of recombinant keratinocyte growth factor during liquid formulation development J. Pharm. Sci. 83 1994 1657-1661
17. S.J. Shire Z. Shahrokh and J. Liu Challenges in the development of high protein concentration formulations J. Pharm. Sci. 93 2004 1390-1402
18. W. Wang Instability, stabilization, and formulation of liquid protein pharmaceuticals Int. J. Pharm. 185 1999 129-188
19. C.M. Won T.E. Molnar R.E. McKean and G. Spenlehauer Stabilizers against heat-induced aggregation of RPR 114849, an acidic fibroblast growth factor (aFGF) Int. J. Pharm. 167 1998 25-36
20. K. Adadevoh M. Croyle D. Malarme E. Bonfils and M.A. Bowe A short-term field use and shipping stability study of a wild type Ad5 adenoviral reference material BioProcessing Fall 2002 62-69
21. G. Qu C. Connolly A. Koblansky J.M. Sommer A. McClelland and J.F. Wright Evidence that ionic interactions are involved in concentration-induced aggregation of recombinant adeno-associated virus Mol. Ther. 7 2003 S238
22. P. Smith J.F. Wright G. Qu S. Patarroyo-White A. Parker and J.M. Sommer Packaging of host cell and plasmid DNA into recombinant adeno-associated virus particles produced by triple transfection Mol. Ther. 7 2003 S348
23. T. Matsushita et al. Adeno-associated virus vectors can be efficiently produced without helper virus Gene Ther. 5 1998 938-945
24. J.F. Wright and G. Qu Large-scale recombinant adeno-associated virus (rAAV) production and purification United States Patent 6,593,123 2003
25. J.M. Sommer et al. Quantification of adeno-associated virus particles and empty capsid by optical density measurement Mol. Ther. 7 2003 122-128