Regulation of gene expression in vivo following transduction by two separate raav vectors


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ABSTRACT Control of gene expression is important to gene therapy for purposes of both dosing and safety. In vivo regulation of gene expression was demonstrated following co-injection of two


separate recombinant adeno-associated virus vectors, one encoding an inducible murine erythropoietin transgene and the other a transcriptional activator, directly into the skeletal muscle of


adult immunocompetent mice. Transcription was controlled by systemic administration or withdrawal of tetracycline over an 18 week period, demonstrating that the two vectors were capable of


transducing the same cell. Cellular or humoral immune responses against the transactivator protein were not detected. Access through your institution Buy or subscribe This is a preview of


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AAV TRANSDUCTION IN MICE THROUGH ENGINEERED RECEPTOR EXPRESSION Article Open access 08 June 2023 LARGE-SCALE DISCOVERY OF POTENT, COMPACT AND ERYTHROID SPECIFIC ENHANCERS FOR GENE THERAPY


VECTORS Article Open access 09 May 2025 VIRAL VECTOR PLATFORMS WITHIN THE GENE THERAPY LANDSCAPE Article Open access 08 February 2021 REFERENCES * Naffakh, N. and Danos, O. 1996. Gene


transfer for erythropoiesis enhancement. _Mol. Med. Today_ 2: 343–348. Article  CAS  PubMed  Google Scholar  * Gossen, M. and Bujard, H. 1992. Tight control of gene expression in mammalian


cells by tetracycline-responsive promotors. _Proc. Natl. Acad. Sci. USA_ 89: 5547–5551. Article  CAS  PubMed  PubMed Central  Google Scholar  * No, D., Yao, T.P. and Evans, R.M. 1996.


Ecdysone-inducible gene expression in mammalian cells and transgenic mice. _Proc. Natl. Acad. Sci. USA_ 93: 3346–3351. Article  CAS  PubMed  PubMed Central  Google Scholar  * Rivera, V.M.,


Clackson, T., Nateson, S., Pollock, R., Amara, J.F., Keenan, T. _et al_. 1996. A humanized system for pharmacological control of gene expression. _Nat. Med._ 2: 1028–1032. Article  CAS 


PubMed  Google Scholar  * Wang, Y., DeMayo, F.J., Tsai, S.Y. and O'Malley, B.W. 1997. Ligand-inducible and liver-specific target gene expression in transgenic mice. _Nat. Biotech._ 15:


239–243. Article  CAS  Google Scholar  * Rinsch, C., Regulier, E., Deglon, N., Dalle, B., Beuzard, Y. and Aebischer, P. 1997. A gene therapy approach to regulated delivery of erythropoietin


as a function of oxygen tension. _Hum. Gene Thar._ 8: 1881–1889. Article  CAS  Google Scholar  * Furth, P.A., St Onge, L., Boger, H., Gruss, P., Gossen, M., Kistner, A., Bujard, H. and


Hennighausen, L. 1994. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promotor. _Proc. Natl. Acad. Sci. USA_ 91: 9302–9306. Article  CAS  PubMed  PubMed


Central  Google Scholar  * Kessler, P.D., Podsakoff, G.M., Chen, X., McQuiston, S.A., Colosi, P.C., Matelis, L.A. _et al_. 1996. Gene delivery to skeletal muscle results in sustained


expression and systemic delivery of a therapeutic protein. _Proc. Natl. Acad. Sci. USA_ 93: 14082–14087. Article  CAS  PubMed  PubMed Central  Google Scholar  * Xiao, X., Li, J. and


Samulski, R.J. 1996. Efficient long-term gene transfer into muscle of immunocompetent mice by an adeno-associated virus vector. _J. Virol._ 70: 8098–8108. CAS  PubMed  PubMed Central  Google


Scholar  * Fisher, K.J., Jooss, K., Alston, J., Yang, Y., Haecker, S.E., High, K. _et al_. 1997. Recombinant adeno-associated virus for muscle directed gene therapy. _Nat. Med._ 3: 306–312.


Article  CAS  PubMed  Google Scholar  * Murphy, J.E., Zhou, S., Giese, K., Williams, L.T., Escobedo, J.A. and Dwarki, V.J. 1997. Long-term correction of obesity and diabetes in genetically


obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin. _Proc. Natl. Acad. Sci. USA_ 94: 13921–13926. Article  CAS  PubMed  PubMed Central


  Google Scholar  * Snyder, R.O., Spratt, S.K., Lagarde, C., Bohl, D., Kaspar, B.K., Sloan, B.S. _et al_. 1997. Efficient and stable AAV-mediated transduction in the skeletal muscle of adult


immunocompetent mice. _Hum. Gene Ther._ 8: 1891–1900. Article  CAS  PubMed  Google Scholar  * Clark, K.R., Sferra, T.J. and Johnson, P.R. 1997. Recombinant adeno-associated viral vectors


mediate long-term transgene expression in muscle. _Hum. Gene Ther._ 8: 659–669. Article  CAS  PubMed  Google Scholar  * Dai, Y., Schwarz, E.M., Gu, D., Zhang, W.-W., Sarvetnick, N. and


Verma, I. 1995. Cellular and humoral immune responses to adenoviral vectors containing factor IX gene: tolerization of factor IX and vector antigens allows for long-term expression. _Proc.


Natl. Acad. Sci. USA_ 92: 1401–1405. Article  CAS  PubMed  PubMed Central  Google Scholar  * Herzog, R.W., Hagstron, J.N., Kung, S.-H., Tai, S.J., Wilson, J.M., Fisher, K.J. and High, K.A.


1997. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. _Proc. Natl. Acad. Sci. USA_ 94:


5804–5809. Article  CAS  PubMed  PubMed Central  Google Scholar  * Hall, Z. and Ralston, E. 1989. Nuclear domains in muscle cells. _Cell_ 59: 771–772. Article  CAS  PubMed  Google Scholar  *


Snyder, R.O., Miao, C.H., Patijn, G.A., Spratt, S.K., Danos, O., Gown, A.M. _et al_. 1997. Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer


of recombinant AAV vectors. _Nat. Genet._ 16: 270–276. Article  CAS  PubMed  Google Scholar  * Flannery, J.G., Zolotukhin, S., Vaquero, M.I., LaVail, M.M., Muzyczka, N. and Hauswirth, W.W.


1997. Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus. _Proc. Natl. Acad. Sci. USA_ 94: 6916–6921. Article  CAS  PubMed  PubMed Central  Google


Scholar  * Dhawan, J., Rando, T.A., Elson, S.L., Bujard, H. and Blau, H.M. 1995. Tetracycline-regulated gene expression following direct gene transfer into mouse skeletal muscle. _Somat.


Cell. Mol. Genet._ 21: 233–240. Article  CAS  PubMed  Google Scholar  * Bohl, D., Naffakh, N. and Heard, J.M. 1997. Long-term control of erythropoietin secretion by doxycycline in mice


transplanted with engineered primary myoblasts. _Nat. Med._ 3: 299–305. Article  CAS  PubMed  Google Scholar  * Kistner, A., Gossen, M., Zimmermann, F., Jerecic, J., Ullmer, C., Lubbert, H.,


and Bujard, H. 1996. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. _Proc. Natl. Acad. Sci. USA_ 93: 10933–10938. Article  CAS  PubMed


  PubMed Central  Google Scholar  * McLaughlin, S.K., Collis, P., Hermonat, P.L. and Muzyczka, N. 1988. Adeno-associated virus general transduction vectors: analysis of proviral structures.


_J. Virol._ 62: 1963–1973. CAS  PubMed  PubMed Central  Google Scholar  * Miao, C.H., Snyder, R.O., Schowalter, D.B., Patijn, G.A., Donahue, B.A., Winther, B. and Kay, M.A. 1998. Kinetics of


rAAV Integration in the Liver. _Nat. Genet._ 19: 13–15. Article  CAS  PubMed  Google Scholar  * Ulmer, J.B., Donnelly, J.J., Parker, S.E., Rhodes, G.H., Feigner, P.L., Dwarki, V.J. _et al_.


1993. Heterologous protection against influenza by injection of DNA encoding a viral protein. _Science_ 259: 1745–1749. Article  CAS  PubMed  Google Scholar  * Manning, W.C., Paliard, X.,


Zhou, S., Bland, M.P., Lee, A.Y., Hong, K. _et al_. 1997. Genetic immunization with adeno-associated virus vectors expressing herpes simplex virus type 2 glycoproteins B and D. _J. Virol._


71: 7960–7962. CAS  PubMed  PubMed Central  Google Scholar  * Mandel, R.J., Rendahl, K.G., Spratt, S.K., Snyder, R.O.L.K. and Leff, S.E. 1998. Characterization of intrastriatal recombinant


adeno-associated virus-mediated gene transfer of human tyrosine hydroxylase and human GTP-Cyclohydrolase I in a rat model of Parkinson's disease. _J. Neurosci._ 18: 4271–4284. Article 


CAS  PubMed  PubMed Central  Google Scholar  * Goodman, S., Xiao, X., Donahue, R., Moulton, A., Miller, J., Walsh, C., Young, N.S., Samulski, R.J. and Nienhuis, A.W. 1994. Recombinant


adeno-associated virus-mediated gene transfer into hematopoietic progenitor cells. _Blood_ 84: 1492–1500. CAS  PubMed  Google Scholar  * McCown, T.J., Xiao, X., Li, J., Breese, G.R. and


Samulski, R.J. 1996. Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. _Brain Res._ 713: 99–107. Article  CAS  PubMed  Google


Scholar  * Hardy, S., Kitamura, M., Harris-Stansil, T., Dai, Y. and Phipps, M.L. 1997. Construction of Adenovirus Vectors through Cre-lox Recombination. _J. Virol._ 71: 1842–1849. CAS 


PubMed  PubMed Central  Google Scholar  * Neering, S.J., Hardy, S.F., Minamoto, D., Spratt, S., and Jordan, C.T. 1996. Transduction of Primitive Human Hematopoietic Cells with Recombinant


Adenovirus Vectors. _Blood_ 88: 1147–1155. CAS  PubMed  Google Scholar  * Kirk, R.E. 1968. _Experimental design: procedures lor the behavioral sciences_. Brooks/Cole, Belmont, CA. Google


Scholar  Download references AUTHOR INFORMATION Author notes * Richard O. Snyder: (e-mail: [email protected]). AUTHORS AND AFFILIATIONS * Cell Genesys Inc., Foster City, CA, 94404


Katherine G. Rendahl, Stuart E. Leff, Gillis R. Otten, Melinda Van Roey, Brian A. Donahue, Ronald J. Mandel & Richard O. Snyder * Institut Pasteur, Laboratoire RTC, Dept.


SIDA/Retrovirus, 75015, Paris, France S. Kaye Spratt, Delphine Bohl, Lawrence K. Cohen & Olivier Danos Authors * Katherine G. Rendahl View author publications You can also search for


this author inPubMed Google Scholar * Stuart E. Leff View author publications You can also search for this author inPubMed Google Scholar * Gillis R. Otten View author publications You can


also search for this author inPubMed Google Scholar * S. Kaye Spratt View author publications You can also search for this author inPubMed Google Scholar * Delphine Bohl View author


publications You can also search for this author inPubMed Google Scholar * Melinda Van Roey View author publications You can also search for this author inPubMed Google Scholar * Brian A.


Donahue View author publications You can also search for this author inPubMed Google Scholar * Lawrence K. Cohen View author publications You can also search for this author inPubMed Google


Scholar * Ronald J. Mandel View author publications You can also search for this author inPubMed Google Scholar * Olivier Danos View author publications You can also search for this author


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ARTICLE CITE THIS ARTICLE Rendahl, K., Leff, S., Otten, G. _et al._ Regulation of gene expression in vivo following transduction by two separate rAAV vectors. _Nat Biotechnol_ 16, 757–761


(1998). https://doi.org/10.1038/nbt0898-757 Download citation * Received: 14 April 1998 * Accepted: 22 June 1998 * Issue Date: 01 August 1998 * DOI: https://doi.org/10.1038/nbt0898-757 SHARE


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