Robert M. Kotin, Ph.D.

Publications

Robert M. Kotin
Senior Investigator

P: +1 301 496 1594
F: +1 301 496 9985
kotinr@nhlbi.nih.gov

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.
Barbash IM, Cecchini S, Faranesh AZ, Virag T, Li L, Yang Y, Hoyt RF, Kornegay JN, Bogan JR, Garcia L, Lederman RJ, Kotin RM.
Gene Ther. 2012 May 3;.
[Text Abstract on PubMed]

Long-term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping.
Bish LT, Sleeper MM, Forbes SC, Wang B, Reynolds C, Singletary GE, Trafny D, Morine KJ, Sanmiguel J, Cecchini S, Virag T, Vulin A, Beley C, Bogan J, Wilson JM, Vandenborne K, Kornegay JN, Walter GA, Kotin RM, Garcia L, Sweeney HL.
Mol. Ther. 2012 Mar;20(3):580-9.
[Text Abstract on PubMed]

Versatile and efficient genome editing in human cells by combining zinc-finger nucleases with adeno-associated viral vectors.
Händel EM, Gellhaus K, Khan K, Bednarski C, Cornu TI, Müller-Lerch F, Kotin RM, Heilbronn R, Cathomen T.
Hum. Gene Ther. 2012 Mar;23(3):321-9.
[Text Abstract on PubMed]

Reproducible high yields of recombinant adeno-associated virus produced using invertebrate cells in 0.02- to 200-liter cultures.
Cecchini S, Virag T, Kotin RM.
Hum. Gene Ther. 2011 Aug;22(8):1021-30.
[Text Abstract on PubMed]

Large-scale recombinant adeno-associated virus production.
Kotin RM.
Hum. Mol. Genet. 2011 Apr 15;20(R1):R2-6.
[Text Abstract on PubMed]

A simplified baculovirus-AAV expression vector system coupled with one-step affinity purification yields high-titer rAAV stocks from insect cells.
Smith RH, Levy JR, Kotin RM.
Mol. Ther. 2009 Nov;17(11):1888-96.
[Text Abstract on PubMed]

Producing recombinant adeno-associated virus in foster cells: overcoming production limitations using a baculovirus-insect cell expression strategy.
Virag T, Cecchini S, Kotin RM.
Hum. Gene Ther. 2009 Aug;20(8):807-17.
[Text Abstract on PubMed]

Evidence of prior exposure to human bocavirus as determined by a retrospective serological study of 404 serum samples from adults in the United States.
Cecchini S, Negrete A, Virag T, Graham BS, Cohen JI, Kotin RM.
Clin. Vaccine Immunol. 2009 May;16(5):597-604.
[Text Abstract on PubMed]

Strategies for manufacturing recombinant adeno-associated virus vectors for gene therapy applications exploiting baculovirus technology.
Negrete A, Kotin RM.
Brief Funct Genomic Proteomic. 2008 Jul;7(4):303-11.
[Text Abstract on PubMed]

Glucose- and metabolically regulated hepatic insulin gene therapy for diabetes.
Hsu PY, Kotin RM, Yang YW.
Pharm. Res. 2008 Jun;25(6):1460-8.
[Text Abstract on PubMed]

Toward exascale production of recombinant adeno-associated virus for gene transfer applications.
Cecchini S, Negrete A, Kotin RM.
Gene Ther. 2008 Jun;15(11):823-30.
[Text Abstract on PubMed]

Chromatography-based purification of adeno-associated virus.
Smith RH, Yang L, Kotin RM.
Methods Mol. Biol. 2008;434:37-54.
[Text Abstract on PubMed]

Large-scale production of recombinant adeno-associated viral vectors.
Negrete A, Kotin RM.
Methods Mol. Biol. 2008;433:79-96.
[Text Abstract on PubMed]

Production of recombinant adeno-associated vectors using two bioreactor configurations at different scales.
Negrete A, Kotin RM.
J. Virol. Methods. 2007 Nov;145(2):155-61.
[Text Abstract on PubMed]

Economized large-scale production of high yield of rAAV for gene therapy applications exploiting baculovirus expression system.
Negrete A, Yang LC, Mendez AF, Levy JR, Kotin RM.
J Gene Med. 2007 Nov;9(11):938-48.
[Text Abstract on PubMed]

Process optimization of large-scale production of recombinant adeno-associated vectors using dielectric spectroscopy.
Negrete A, Esteban G, Kotin RM.
Appl. Microbiol. Biotechnol. 2007 Sep;76(4):761-72.
[Text Abstract on PubMed]

Real-time imaging of convection-enhanced delivery of viruses and virus-sized particles.
Szerlip NJ, Walbridge S, Yang L, Morrison PF, Degen JW, Jarrell ST, Kouri J, Kerr PB, Kotin R, Oldfield EH, Lonser RR.
J. Neurosurg. 2007 Sep;107(3):560-7.
[Text Abstract on PubMed]

Recombinant adeno-associated virus vector for gene transfer to the transplanted rat heart.
Schirmer JM, Miyagi N, Rao VP, Ricci D, Federspiel MJ, Kotin RM, Russell SJ, McGregor CG.
Transpl. Int. 2007 Jun;20(6):550-7.
[Text Abstract on PubMed]

Development of recombinant adeno-associated virus vectors carrying small interfering RNA (shHec1)-mediated depletion of kinetochore Hec1 protein in tumor cells.
Li L, Yang L, Scudiero DA, Miller SA, Yu ZX, Stukenberg PT, Shoemaker RH, Kotin RM.
Gene Ther. 2007 May;14(10):814-27.
[Text Abstract on PubMed]

Adeno-associated virus (AAV) serotypes 2, 4 and 5 display similar transduction profiles and penetrate solid tumor tissue in models of human glioma.
Thorsen F, Afione S, Huszthy PC, Tysnes BB, Svendsen A, Bjerkvig R, Kotin RM, Lønning PE, Hoover F.
J Gene Med. 2006 Sep;8(9):1131-40.
[Text Abstract on PubMed]

Scalable generation of high-titer recombinant adeno-associated virus type 5 in insect cells.
Urabe M, Nakakura T, Xin KQ, Obara Y, Mizukami H, Kume A, Kotin RM, Ozawa K.
J. Virol. 2006 Feb;80(4):1874-85.
[Text Abstract on PubMed]

Profiles of PrKX expression in developmental mouse embryo and human tissues.
Li W, Yu ZX, Kotin RM.
J. Histochem. Cytochem. 2005 Aug;53(8):1003-9.
[Text Abstract on PubMed]

RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model.
Harper SQ, Staber PD, He X, Eliason SL, Martins IH, Mao Q, Yang L, Kotin RM, Paulson HL, Davidson BL.
Proc. Natl. Acad. Sci. U.S.A. 2005 Apr 19;102(16):5820-5.
[Text Abstract on PubMed]

The DNA minor groove binding agents Hoechst 33258 and 33342 enhance recombinant adeno-associated virus (rAAV) transgene expression.
Li L, Yang L, Kotin RM.
J Gene Med. 2005 Apr;7(4):420-31.
[Text Abstract on PubMed]

Widespread dispersion of adeno-associated virus serotype 1 and adeno-associated virus serotype 6 vectors in the rat central nervous system and in human glioblastoma multiforme xenografts.
Huszthy PC, Svendsen A, Wilson JM, Kotin RM, Lønning PE, Bjerkvig R, Hoover F.
Hum. Gene Ther. 2005 Mar;16(3):381-92.
[Text Abstract on PubMed]

RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia.
Xia H, Mao Q, Eliason SL, Harper SQ, Martins IH, Orr HT, Paulson HL, Yang L, Kotin RM, Davidson BL.
Nat. Med. 2004 Aug;10(8):816-20.
[Text Abstract on PubMed]

The nuclease domain of adeno-associated virus rep coordinates replication initiation using two distinct DNA recognition interfaces.
Hickman AB, Ronning DR, Perez ZN, Kotin RM, Dyda F.
Mol. Cell. 2004 Feb 13;13(3):403-14.
[Text Abstract on PubMed]

Serum-free production and column purification of adeno-associated virus type 5.
Smith RH, Ding C, Kotin RM.
J. Virol. Methods. 2003 Dec;114(2):115-24.
[Text Abstract on PubMed]

Adeno-associated virus type 5: transduction efficiency and cell-type specificity in the primate retina.
Lotery AJ, Yang GS, Mullins RF, Russell SR, Schmidt M, Stone EM, Lindbloom JD, Chiorini JA, Kotin RM, Davidson BL.
Hum. Gene Ther. 2003 Nov 20;14(17):1663-71.
[Text Abstract on PubMed]

Insect cells as a factory to produce adeno-associated virus type 2 vectors.
Urabe M, Ding C, Kotin RM.
Hum. Gene Ther. 2002 Nov 1;13(16):1935-43.
[Text Abstract on PubMed]

Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size.
Yang GS, Schmidt M, Yan Z, Lindbloom JD, Harding TC, Donahue BA, Engelhardt JF, Kotin R, Davidson BL.
J. Virol. 2002 Aug;76(15):7651-60.
[Text Abstract on PubMed]

Immunological aspects of recombinant adeno-associated virus delivery to the mammalian brain.
Mastakov MY, Baer K, Symes CW, Leichtlein CB, Kotin RM, During MJ.
J. Virol. 2002 Aug;76(16):8446-54.
[Text Abstract on PubMed]

Structural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus Rep.
Hickman AB, Ronning DR, Kotin RM, Dyda F.
Mol. Cell. 2002 Aug;10(2):327-37.
[Text Abstract on PubMed]

Transposase-mediated construction of an integrated adeno-associated virus type 5 helper plasmid.
Smith RH, Afione SA, Kotin RM.
BioTechniques. 2002 Jul;33(1):204-6, 208, 210-1.
[Text Abstract on PubMed]

Recombinant adeno-associated virus serotypes 2- and 5-mediated gene transfer in the mammalian brain: quantitative analysis of heparin co-infusion.
Mastakov MY, Baer K, Kotin RM, During MJ.
Mol. Ther. 2002 Apr;5(4):371-80.
[Text Abstract on PubMed]

Adeno-associated virus type 2 Rep78 inhibition of PKA and PRKX: fine mapping and analysis of mechanism.
Schmidt M, Chiorini JA, Afione S, Kotin R.
J. Virol. 2002 Feb;76(3):1033-42.
[Text Abstract on PubMed]

Recombinant adeno-associated virus serotype 2 vectors mediate stable interleukin 10 secretion from salivary glands into the bloodstream.
Yamano S, Huang LY, Ding C, Chiorini JA, Goldsmith CM, Wellner RB, Golding B, Kotin RM, Scott DE, Baum BJ.
Hum. Gene Ther. 2002 Jan 20;13(2):287-98.
[Text Abstract on PubMed]

Biochemical characterization of Junonia coenia densovirus nonstructural protein NS-1.
Ding C, Urabe M, Bergoin M, Kotin RM.
J. Virol. 2002 Jan;76(1):338-45.
[Text Abstract on PubMed]

Adeno-associated virus type 2 Rep78 induces apoptosis through caspase activation independently of p53.
Schmidt M, Afione S, Kotin RM.
J. Virol. 2000 Oct;74(20):9441-50.
[Text Abstract on PubMed]

Glucose-responsive gene delivery in pancreatic Islet cells via recombinant adeno-associated viral vectors.
Yang YW, Kotin RM.
Pharm. Res. 2000 Sep;17(9):1056-61.
[Text Abstract on PubMed]

An adeno-associated virus (AAV) initiator protein, Rep78, catalyzes the cleavage and ligation of single-stranded AAV ori DNA.
Smith RH, Kotin RM.
J. Virol. 2000 Apr;74(7):3122-9.
[Text Abstract on PubMed]

Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer.
Zabner J, Seiler M, Walters R, Kotin RM, Fulgeras W, Davidson BL, Chiorini JA.
J. Virol. 2000 Apr;74(8):3852-8.
[Text Abstract on PubMed]

Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system.
Davidson BL, Stein CS, Heth JA, Martins I, Kotin RM, Derksen TA, Zabner J, Ghodsi A, Chiorini JA.
Proc. Natl. Acad. Sci. U.S.A. 2000 Mar 28;97(7):3428-32.
[Text Abstract on PubMed]

Adeno-associated virus (AAV) type 5 Rep protein cleaves a unique terminal resolution site compared with other AAV serotypes.
Chiorini JA, Afione S, Kotin RM.
J. Virol. 1999 May;73(5):4293-8.
[Text Abstract on PubMed]

PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase regulated by the regulatory subunit type I.
Zimmermann B, Chiorini JA, Ma Y, Kotin RM, Herberg FW.
J. Biol. Chem. 1999 Feb 26;274(9):5370-8.
[Text Abstract on PubMed]

Cloning and characterization of adeno-associated virus type 5.
Chiorini JA, Kim F, Yang L, Kotin RM.
J. Virol. 1999 Feb;73(2):1309-19.
[Text Abstract on PubMed]

Adenoassociated virus-mediated transfer of a functional water channel into salivary epithelial cells in vitro and in vivo.
Braddon VR, Chiorini JA, Wang S, Kotin RM, Baum BJ.
Hum. Gene Ther. 1998 Dec 10;9(18):2777-85.
[Text Abstract on PubMed]

Inhibition of PrKX, a novel protein kinase, and the cyclic AMP-dependent protein kinase PKA by the regulatory proteins of adeno-associated virus type 2.
Chiorini JA, Zimmermann B, Yang L, Smith RH, Ahearn A, Herberg F, Kotin RM.
Mol. Cell. Biol. 1998 Oct;18(10):5921-9.
[Text Abstract on PubMed]

Recombinant adeno-associated virus for the generation of autologous, gene-modified tumor vaccines: evidence for a high transduction efficiency into primary epithelial cancer cells.
Maass G, Bogedain C, Scheer U, Michl D, Hörer M, Braun-Falco M, Volkenandt M, Schadendorf D, Wendtner CM, Winnacker EL, Kotin RM, Hallek M.
Hum. Gene Ther. 1998 May 1;9(7):1049-59.
[Text Abstract on PubMed]

Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles.
Chiorini JA, Yang L, Liu Y, Safer B, Kotin RM.
J. Virol. 1997 Sep;71(9):6823-33.
[Text Abstract on PubMed]

Gene transfer of the costimulatory molecules B7-1 and B7-2 into human multiple myeloma cells by recombinant adeno-associated virus enhances the cytolytic T cell response.
Wendtner CM, Nolte A, Mangold E, Buhmann R, Maass G, Chiorini JA, Winnacker EL, Emmerich B, Kotin RM, Hallek M.
Gene Ther. 1997 Jul;4(7):726-35.
[Text Abstract on PubMed]

The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a hexameric complex in the presence of AAV ori sequences.
Smith RH, Spano AJ, Kotin RM.
J. Virol. 1997 Jun;71(6):4461-71.
[Text Abstract on PubMed]

The roles of AAV Rep proteins in gene expression and targeted integration.
Chiorini JA, Wiener SM, Yang L, Smith RH, Safer B, Kilcoin NP, Liu Y, Urcelay E, Kotin RM.
Curr. Top. Microbiol. Immunol. 1996;218:25-33.
[Text Abstract on PubMed]

High-efficiency transfer of the T cell co-stimulatory molecule B7-2 to lymphoid cells using high-titer recombinant adeno-associated virus vectors.
Chiorini JA, Wendtner CM, Urcelay E, Safer B, Hallek M, Kotin RM.
Hum. Gene Ther. 1995 Dec;6(12):1531-41.
[Text Abstract on PubMed]

Determination of adeno-associated virus Rep68 and Rep78 binding sites by random sequence oligonucleotide selection.
Chiorini JA, Yang L, Safer B, Kotin RM.
J. Virol. 1995 Nov;69(11):7334-8.
[Text Abstract on PubMed]

Asymmetric replication in vitro from a human sequence element is dependent on adeno-associated virus Rep protein.
Urcelay E, Ward P, Wiener SM, Safer B, Kotin RM.
J. Virol. 1995 Apr;69(4):2038-46.
[Text Abstract on PubMed]

Sequence requirements for stable binding and function of Rep68 on the adeno-associated virus type 2 inverted terminal repeats.
Chiorini JA, Wiener SM, Owens RA, Kyöstió SR, Kotin RM, Safer B.
J. Virol. 1994 Nov;68(11):7448-57.
[Text Abstract on PubMed]

The regulatory rep protein of adeno-associated virus binds to sequences within the c-H-ras promoter.
Batchu RB, Kotin RM, Hermonat PL.
Cancer Lett. 1994 Oct 28;86(1):23-31.
[Text Abstract on PubMed]

Adeno-associated virus DNA replication in vitro: activation by a maltose binding protein/Rep 68 fusion protein.
Ward P, Urcelay E, Kotin R, Safer B, Berns KI.
J. Virol. 1994 Sep;68(9):6029-37.
[Text Abstract on PubMed]

Prospects for the use of adeno-associated virus as a vector for human gene therapy.
Kotin RM.
Hum. Gene Ther. 1994 Jul;5(7):793-801.
[Text Abstract on PubMed]

Adeno-associated virus (AAV) Rep proteins mediate complex formation between AAV DNA and its integration site in human DNA.
Weitzman MD, Kyöstiö SR, Kotin RM, Owens RA.
Proc. Natl. Acad. Sci. U.S.A. 1994 Jun 21;91(13):5808-12.
[Text Abstract on PubMed]

Biologically active Rep proteins of adeno-associated virus type 2 produced as fusion proteins in Escherichia coli.
Chiorini JA, Weitzman MD, Owens RA, Urcelay E, Safer B, Kotin RM.
J. Virol. 1994 Feb;68(2):797-804.
[Text Abstract on PubMed]

Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination.
Kotin RM, Linden RM, Berns KI.
EMBO J. 1992 Dec;11(13):5071-8.
[Text Abstract on PubMed]

Mapping and direct visualization of a region-specific viral DNA integration site on chromosome 19q13-qter.
Kotin RM, Menninger JC, Ward DC, Berns KI.
Genomics. 1991 Jul;10(3):831-4.
[Text Abstract on PubMed]

Site-specific integration by adeno-associated virus.
Kotin RM, Siniscalco M, Samulski RJ, Zhu XD, Hunter L, Laughlin CA, McLaughlin S, Muzyczka N, Rocchi M, Berns KI.
Proc. Natl. Acad. Sci. U.S.A. 1990 Mar;87(6):2211-5.
[Text Abstract on PubMed]

Organization of adeno-associated virus DNA in latently infected Detroit 6 cells.
Kotin RM, Berns KI.
Virology. 1989 Jun;170(2):460-7.
[Text Abstract on PubMed]

Regulation of adeno-associated virus DNA replication.
Berns KI, Kotin RM, Labow MA.
Biochim. Biophys. Acta. 1988 Dec 20;951(2-3):425-9.
[Text Abstract on PubMed]

Ribonuclease structure and catalysis: effects of crystalline enzyme, alcohol cryosolvents, low temperatures, and product inhibition.
Fink AL, Kar D, Kotin R.
Biochemistry. 1987 Dec 29;26(26):8571-9.
[Text Abstract on PubMed]

Evidence that the methylation inhibitor cycloleucine causes accumulation of a discrete ribosomal RNA precursor in hamster mitochondria.
Prince DL, Kotin RM, Dubin DT.
Mol. Biol. Rep. 1986;11(1):51-5.
[Text Abstract on PubMed]

Sequences of the coding and flanking regions of the large ribosomal subunit RNA gene of mosquito mitochondria.
HsuChen CC, Kotin RM, Dubin DT.
Nucleic Acids Res. 1984 Oct 25;12(20):7771-85.
[Text Abstract on PubMed]