Transient transfection methods for clinical adeno-associated viral vector production
Open accessAbstract
Recombinant adeno-associated virus (AAV)-based vectors expressing therapeutic gene products have shown great potential for human gene therapy. One major challenge for translation of promising research to clinical development is the manufacture of sufficient quantities of AAV vectors that meet stringent standards for purity, potency, and safety required for human parenteral administration. Several methods have been developed to generate recombinant AAV in cell culture, each offering distinct advantages. Transient transfection-based methods for vector production are reviewed here, with a focus on specific considerations for development of AAV vectors as clinical products.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
To date, only viral vectors used in gene therapy have been produced by transient transfections for clinical applications.
“To date, only viral vectors used in gene therapy have been produced by transient transfections for clinical applications (Wright, 2009).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Wright, 2009
The paper’s opening section describes transient transfection-based methods for generating clinical-grade AAV vectors, which are viral vectors used in gene therapy. It does not establish the claim’s exclusivity—that only gene-therapy viral vectors had been produced this way for clinical applications. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis
Maguire, A. M., Simonelli, F., Pierce, E. A., Pugh, E. N., Mingozzi, F., Bennicelli, J., Banfi, S., Marshall, K. A., Testa, F., Surace, E. M., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802315 · Cited by 2,145 · see citing works
Self-citationManufacturing and characterizing AAV-based vectors for use in clinical studies
Wright, J. F. (2008) · Gene Therapy · doi:10.1038/gt.2008.65 · Cited by 205 · see citing works
Self-citationGrimm, D., Kern, A., Pawlita, M., Ferrari, F. K., Samulski, R. J., & Kleinschmidt, J. A. (1999) · Gene Therapy · doi:10.1038/sj.gt.3300946 · Cited by 195 · see citing works
Wang, X. S., Qing, K., Ponnazhagan, S., & Srivastava, A. (1997) · Journal of Virology · doi:10.1128/jvi.71.4.3077-3082.1997 · Cited by 61 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Berns, K.I., and Parrish, C.R. (2007). Parvoviridae. In D.M. Knipe, P.M. Howley, D.E. Griffin, R.A. Lamb, and M.A. Martin, eds. Fields Virology , 5th ed. (Lippincott Williams & Wilkins, Philadelphia) pp. 2437-2477.
- Boussif, O., Lezoualc'h, F., Zanta, M.A., Mergny, M.D., Scherman, D., Demeneix, B., and Behr, J.-P. (1995). A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo : Polyethylenimine. Proc. Natl. Acad. Sci. U.S.A. 92, 7297-7301.
- Felgner, P.L., Gadek, T.R., Holm, M., Roman, R., Chan, H.W., Wenz, M., Northrop, J.P., Ringold, G.M., and Danielsen, M. (1987). Lipofection: A highly efficient, lipid-mediated DNAtransfection procedure. Proc. Natl. Acad. Sci. U.S.A. 84, 74137417.
- Food and Drug Administration, U.S. Department of Health and Human Services. (1998). International conference on harmonisation; guidance on viral safety evaluation of biotechnology products derived from cell lines of human or animal origin. Fed. Regist. 63, 51074-51084. Available at http: = = www.fda. gov = cber = gdlns = virsafe.pdf (accessed May 2009).
- Recombinant DNA Advisory Committee, National Institutes of Health. (2007). AAV Symposium: Immune Responses to Adeno-Associated Virus (AAV) Vectors. Available at http: = = www4.od.nih.gov = oba = RAC = meeting.html (accessed May 2009).
Cited by
Sorted by citations
Russell, S., Bennett, J., Wellman, J. A., Chung, D. C., Yu, Z.-F., Tillman, A., Wittes, J., Pappas, J., Elci, O., McCague, S., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31868-8 · Cited by 1,952 · see citing works
Self-citationAdeno-Associated Virus (AAV) as a Vector for Gene Therapy
Naso, M. F., Tomkowicz, B., Perry, W. L., & Strohl, W. R. (2017) · BioDrugs · doi:10.1007/s40259-017-0234-5 · Cited by 1,362 · see citing works
Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
Manufacturing of recombinant adeno-associated viral vectors for clinical trials
Clément, N., & Grieger, J. C. (2016) · Molecular Therapy - Methods & Clinical Development · doi:10.1038/mtm.2016.2 · Cited by 286 · see citing works
Cukras, C., Wiley, H. E., Jeffrey, B. G., Sen, H. N., Turriff, A., Zeng, Y., Vijayasarathy, C., Marangoni, D., Ziccardi, L., Kjellstrom, S., et al. (2018) · Molecular Therapy · doi:10.1016/j.ymthe.2018.05.025 · Cited by 268 · see citing works
“The vector was generated by triple transfection and purified by combined column chromatography and cesium chloride gradient ultracentrifugation to remove empty capsids.(31) The final product was diluted to appropriate concentration for delivery in 50 mL total volume into the study eye by intravitreal injection using a…”
MethodSelf-citationProduction of adeno-associated virus vectors for in vitro and in vivo applications
Kimura, T., Ferran, B., Tsukahara, Y., Shang, Q., Desai, S., Fedoce, A., Pimentel, D. R., Luptak, I., Adachi, T., Ido, Y., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-49624-w · Cited by 155 · see citing works
Hareendran, S., Balakrishnan, B., Sen, D., Kumar, S., Srivastava, A., & Jayandharan, G. R. (2013) · Reviews in Medical Virology · doi:10.1002/rmv.1762 · Cited by 113 · see citing works
Manufacturing of recombinant adeno-associated viruses using mammalian expression platforms
Robert, M., Chahal, P. S., Audy, A., Kamen, A., Gilbert, R., & Gaillet, B. (2017) · Biotechnology Journal · doi:10.1002/biot.201600193 · Cited by 89 · see citing works
Adeno-associated Virus: A Key to the Human Genome?
Henckaerts, E., & Linden, R. M. (2010) · Future Virology · doi:10.2217/fvl.10.48 · Cited by 71 · see citing works
Manufacturing Clinical Grade Recombinant Adeno-Associated Virus Using Invertebrate Cell Lines
Kotin, R. M., & Snyder, R. O. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.042 · Cited by 59 · see citing works
Denard, J., Marolleau, B., Jenny, C., Rao, T. N., Fehling, H. J., Voit, T., & Svinartchouk, F. (2013) · Journal of Virology · doi:10.1128/jvi.01813-13 · Cited by 31 · see citing works
- Authors
- Wright, J. F.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Wright, J. Fraser
- ORCID
- Wright, J. Fraser
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2009-07
- Volume
- 20
- Issue
- 7
- Pages
- 698-706
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- PMC
- PMC2829280
- OpenAlex
- W2129666112
- Cited by
- 131
- References
- 4
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 9 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 7 · 2018: 6 · 2017: 12 · 2016: 1 · 2015: 5 · 2014: 10 · 2013: 6 · 2012: 2
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Gene Therapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- adeno-associated virus vectors, transient transfection, recombinant AAV production, cell culture production
- MeSH terms
- Dependovirus, Genetic Engineering, Genetic Vectors, Humans, Transfection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
