AAV2 production with optimized N/P ratio and PEI-mediated transfection results in low toxicity and high titer for in vitro and in vivo applications

Journal of Virological Methods

Volumn 193, Issue 2, 2013, Pages 270-277

  Huang, Xinping ^a   Hartley, Antja Voy ^a   Yin, Yishi ^a   Herskowitz, Jeremy H ^a   Lah, James J ^a   Ressler, Kerry J ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

AAV; AAV2 GFP; N P ratio; Optimization; Polyethylenimine (PEI); Recombinant virus

Indexed keywords

IODIXANOL; PARVOVIRUS VECTOR; POLYETHYLENEIMINE; VIRUS DNA;

ADENO ASSOCIATED VIRUS; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN; CELL CULTURE; CONTROLLED STUDY; COST EFFECTIVENESS ANALYSIS; DENSITY GRADIENT CENTRIFUGATION; EMBRYO; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NEWBORN; NONHUMAN; PLASMID; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; VIRUS ASSEMBLY; VIRUS GENOME; VIRUS INFECTION; VIRUS RECOMBINANT; VIRUS REPLICATION; VIRUS STRAIN;

AAV; AAV2-GFP; N/P RATIO; OPTIMIZATION; POLYETHYLENIMINE (PEI); RECOMBINANT VIRUS;

CELL LINE; CENTRIFUGATION, DENSITY GRADIENT; DEPENDOVIRUS; DIALYSIS; HUMANS; NITROGEN; PHOSPHORUS; POLYETHYLENEIMINE; TRANSFECTION; VIRAL LOAD; VIRUS CULTIVATION;

EID: 84880683587     PISSN: 01660934     EISSN: 18790984     Source Type: Journal    
DOI: 10.1016/j.jviromet.2013.06.008     Document Type: Article

References (36)

1. Atkinson E.M., Debelak D.J., Hart L.A., Reynolds T.C. A high-throughput hybridization method for titer determination of viruses and gene therapy vectors. Nucl. Acids Res. 1998, 26:2821-2823.
2. Ayuso E., Mingozzi F., Montane J., Leon X., Anguela X.M., Haurigot V., Edmonson S.A., Africa L., Zhou S., High K.A., Bosch F., Wright J.F. High AAV vector purity results in serotype- and tissue-independent enhancement of transduction efficiency. Gene Ther. 2010, 17:503-510.
3. Bainbridge J.W., Smith A.J., Barker S.S., Robbie S., Henderson R., Balaggan K., Viswanathan A., Holder G.E., Stockman A., Tyler N., Petersen-Jones S., Bhattacharya S.S., Thrasher A.J., Fitzke F.W., Carter B.J., Rubin G.S., Moore A.T., Ali R.R. Effect of gene therapy on visual function in Leber's congenital amaurosis. N. Engl. J. Med. 2008, 358:2231-2239.
4. Behr J.P. The proton sponge: a trick to enter cells the viruses did not exploit. Chimia 1997, 51:34-36.
5. Boeckle S., von Gersdorff K., van der Piepen S., Culmsee C., Wagner E., Ogris M. Purification of polyethylenimine polyplexes highlights the role of free polycations in gene transfer. J. Gene Med. 2004, 6:1102-1111.
6. Boussif O., Lezoualc'h F., Zanta M.A., Mergny M.D., Scherman D., Demeneix B., Behr J.P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc. Natl. Acad. Sci. U.S.A. 1995, 92:7297-7301.
7. Boussif O., Lezoualch F., Zanta M.A., Mergny M.D., Scherman D., Demeneix B., Behr J.P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo - polyethylenimine. Proc. Natl. Acad. Sci. U.S.A. 1995, 92:7297-7301.
8. Bowles D.E., McPhee S.W.J., Li C.W., Gray S.J., Samulski J.J., Camp A.S., Li J., Wang B., Monahan P.E., Rabinowitz J.E., Grieger J.C., Govindasamy L., Agbandje-McKenna M., Xiao X., Samulski R.J. Phase 1 gene therapy for duchenne muscular dystrophy using a translational optimized AAV vector. Mol. Ther. 2012, 20:443-455.
9. Clamme J.P., Azoulay J., Mely Y. Monitoring of the formation and dissociation of polyethylenimine/DNA complexes by two photon fluorescence correlation spectroscopy. Biophys. J. 2003, 84:1960-1968.
10. Clamme J.P., Krishnamoorthy G., Mely Y. Intracellular dynamics of the gene delivery vehicle polyethylenimine during transfection: investigation by two-photon fluorescence correlation spectroscopy. Biochim. Et Biophy. Acta Biomembr. 2003, 1617:52-61.
11. Durocher Y., Pham P.L., St-Laurent G., Jacob D., Cass B., Chahal P., Lau C.J., Nalbantoglu J., Kamen A. Scalable serum-free production of recombinant adeno-associated virus type 2 by transfection of 293 suspension cells. J. Virol. Methods 2007, 144:32-40.
12. Godbey W.T., Wu K.K., Mikos A.G. Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proc. Natl. Acad. Sci. U.S.A. 1999, 96:5177-5181.
13. Graham F.L., Vandereb A.J. New technique for assay of infectivity of human adenovirus 5 DNA. Virology 1973, 52:456-467.
14. Grimm D., Kay M.A., Kleinschmidt J.A. Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1-6. Mol. Ther. 2003, 7:839-850.
15. Guo P., El-Gohary Y., Prasadan K., Shiota C., Xiao X.W., Wiersch J., Paredes J., Tulachan S., Gittes G.K. Rapid and simplified purification of recombinant adeno-associated virus. J. Virol. Methods 2012, 183:139-146.
16. Hoggan M.D., Blacklow N.R., Rowe W.P. Studies of small DNA viruses found in various adenovirus preparations - physical biological and immunological characteristics. Proc. Natl. Acad. Sci. U.S.A. 1966, 55:1467.
17. Hou S., Ziebacz N., Wieczorek S.A., Kalwarczyk E., Sashuk V., Kalwarczyk T., Kaminski T.S., Holyst R. Formation and structure of PEI/DNA complexes: quantitative analysis. Soft Matter 2011, 7:6967-6972.
18. Jayandharan G.R., Aslanidi G., Martino A.T., Jahn S.C., Perrin G.Q., Herzog R.W., Srivastava A. Activation of the NF-kappaB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy. Proc. Natl. Acad. Sci. U.S.A 2011, 108:3743-3748.
19. Kaplitt M.G., Feigin A., Tang C., Fitzsimons H.L., Mattis P., Lawlor P.A., Bland R.J., Young D., Strybing K., Eidelberg D., During M.J. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet 2007, 369:2097-2105.
20. Kiyota T., Yamamoto M., Schroder B., Jacobsen M.T., Swan R.J., Lambert M.P., Klein W.L., Gendelman H.E., Ransohoff R.M., Ikezu T. AAV1/2-mediated CNS gene delivery of dominant-negative CCL2 mutant suppresses gliosis, beta-amyloidosis, and learning impairment of APP/PS1 mice. Mol. Ther. 2009, 17:803-809.
21. Li J., Daly T.M. Adeno-associated virus-mediated gene transfer to the neonatal brain. Methods 2002, 28:203-207.
22. Lock M., Alvira M., Vandenberghe L.H., Samanta A., Toelen J., Debyser Z., Wilson J.M. Rapid, simple, and versatile manufacturing of recombinant adeno-associated viral vectors at scale. Hum. Gene Ther. 2010, 21:1259-1271.
23. Niemeyer G.P., Herzog R.W., Mount J., Arruda V.R., Tillson D.M., Hathcock J., van Ginkel F.W., High K.A., Lothrop C.D. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood 2009, 113:797-806.
24. Ogris M., Steinlein P., Kursa M., Mechtler K., Kircheis R., Wagner E. The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells. Gene Ther. 1998, 5:1425-1433.
25. Passini M.A., Watson D.J., Vite C.H., Landsburg D.J., Feigenbaum A.L., Wolfe J.H. Intraventricular brain injection of adeno-associated virus type 1 (AAV1) in neonatal mice results in complementary patterns of neuronal transduction to AAV2 and total long-term correction of storage lesions in the brains of beta-glucuronidase-deficient mice. J. Virol. 2003, 77:7034-7040.
26. Pranski E.L., Van Sanford C.D., Dalal N.V., Orr A.L., Karmali D., Cooper D.S., Costa N., Heilman C.J., Gearing M., Lah J.J., Levey A.I., Betarbet R.S. Comparative distribution of protein components of the A20 ubiquitin-editing complex in normal human brain. Neurosci. Lett. 2012, 520:104-109.
27. Reed S.E., Staley E.M., Mayginnes J.P., Pintel D.J., Tullis G.E. Transfection of mammalian cells using linear polyethylenimine is a simple and effective means of producing recombinant adeno-associated virus vectors. J. Virol. Methods 2006, 138:85-98.
28. Rohr U.P., Wulf M.A., Stahn S., Steidl U., Haas R., Kronenwett R. Fast and reliable titration of recombinant adeno-associated virus type-2 using quantitative real-time PCR. J. Virol. Methods 2002, 106:81-88.
29. Thomas M., Ge Q., Lu J.J., Chen J., Klibanov A.M. Cross-linked small polyethylenimines: while still nontoxic, deliver DNA efficiently to mammalian cells in vitro and in vivo. Pharm. Res. 2005, 22:373-380.
30. Thomas M., Ge Q., Lu J.J., Chen J.Z., Klibanov A.M. Cross-linked small polyethylenimines: while still nontoxic, deliver DNA efficiently to mammalian cells in vitro and in vivo. Pharm. Res. 2005, 22:373-380.
31. Vandenberghe L.H., Xiao R., Lock M., Lin J.P., Korn M., Wilson J.M. Efficient serotype-dependent release of functional vector into the culture medium during adeno-associated virus manufacturing. Hum. Gene Ther. 2010, 21:1251-1257.
32. Wright J.F. Transient transfection methods for clinical adeno-associated viral vector production. Hum. Gene Ther. 2009, 20:698-706.
33. Xiao X., Li J., Samulski R.J. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J. Virol. 1998, 72:2224-2232.
34. Zhang C., Yadava P., Hughes J. Polyethylenimine strategies for plasmid delivery to brain-derived cells. Methods 2004, 33:144-150.
35. Zhen Z., Espinoza Y., Bleu T., Sommer J.M., Wright J.F. Infectious titer assay for adeno-associated virus vectors with sensitivity sufficient to detect single infectious events. Hum. Gene Ther. 2004, 15:709-715.
36. Zolotukhin S., Byrne B.J., Mason E., Zolotukhin I., Potter M., Chesnut K., Summerford C., Samulski R.J., Muzyczka N. Recombinant adeno-associated virus purification using novel methods improves infectious titer and yield. Gene Ther. 1999, 6:973-985.