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Robert M Kotin PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentMicrobiology and Physiological Systems
AddressUniversity of Massachusetts Medical School
55 Lake Ave North
Worcester MA 01605
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentMicrobiology and Physiological Systems


    Collapse Biography 
    Collapse education and training
    University of California, Santa Cruz, Santa Cruz, CA, United StatesBABiology
    Rutgers University, New Brunswick, NJ, United StatesPHDMicrobiology

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Smith RH, Hallwirth CV, Westerman M, Hetherington NA, Tseng YS, Cecchini S, Virag T, Ziegler ML, Rogozin IB, Koonin EV, Agbandje-McKenna M, Kotin RM, Alexander IE. Germline viral "fossils" guide in silico reconstruction of a mid-Cenozoic era marsupial adeno-associated virus. Sci Rep. 2016 Jul 05; 6:28965. PMID: 27377618.
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    2. Choudhury SR, Fitzpatrick Z, Harris AF, Maitland SA, Ferreira JS, Zhang Y, Ma S, Sharma RB, Gray-Edwards HL, Johnson JA, Johnson AK, Alonso LC, Punzo C, Wagner KR, Maguire CA, Kotin RM, Martin DR, Sena-Esteves M. In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and Muscle Gene Therapy. Mol Ther. 2016 Aug; 24(7):1247-57. PMID: 27117222.
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    3. Le Guiner C, Montus M, Servais L, Cherel Y, Francois V, Thibaud JL, Wary C, Matot B, Larcher T, Guigand L, Dutilleul M, Domenger C, Allais M, Beuvin M, Moraux A, Le Duff J, Devaux M, Jaulin N, Guilbaud M, Latournerie V, Veron P, Boutin S, Leborgne C, Desgue D, Deschamps JY, Moullec S, Fromes Y, Vulin A, Smith RH, Laroudie N, Barnay-Toutain F, Rivière C, Bucher S, Le TH, Delaunay N, Gasmi M, Kotin RM, Bonne G, Adjali O, Masurier C, Hogrel JY, Carlier P, Moullier P, Voit T. Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients. Mol Ther. 2014 Nov; 22(11):1923-35. PMID: 25200009.
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    4. Li L, Dimitriadis EK, Yang Y, Li J, Yuan Z, Qiao C, Beley C, Smith RH, Garcia L, Kotin RM. Production and characterization of novel recombinant adeno-associated virus replicative-form genomes: a eukaryotic source of DNA for gene transfer. PLoS One. 2013; 8(8):e69879. PMID: 23936358.
      View in: PubMed
    5. Airenne KJ, Hu YC, Kost TA, Smith RH, Kotin RM, Ono C, Matsuura Y, Wang S, Ylä-Herttuala S. Baculovirus: an insect-derived vector for diverse gene transfer applications. Mol Ther. 2013 Apr; 21(4):739-49. PMID: 23439502.
      View in: PubMed
    6. Barbash IM, Cecchini S, Faranesh AZ, Virag T, Li L, Yang Y, Hoyt RF, Kornegay JN, Bogan JR, Garcia L, Lederman RJ, Kotin RM. MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Gene Ther. 2013 Mar; 20(3):274-82. PMID: 22551778.
      View in: PubMed
    7. Denard J, Beley C, Kotin R, Lai-Kuen R, Blot S, Leh H, Asokan A, Samulski RJ, Moullier P, Voit T, Garcia L, Svinartchouk F. Human galectin 3 binding protein interacts with recombinant adeno-associated virus type 6. J Virol. 2012 Jun; 86(12):6620-31. PMID: 22496229.
      View in: PubMed
    8. Händel EM, Gellhaus K, Khan K, Bednarski C, Cornu TI, Müller-Lerch F, Kotin RM, Heilbronn R, Cathomen T. Versatile and efficient genome editing in human cells by combining zinc-finger nucleases with adeno-associated viral vectors. Hum Gene Ther. 2012 Mar; 23(3):321-9. PMID: 21980922.
      View in: PubMed
    9. 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. Long-term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping. Mol Ther. 2012 Mar; 20(3):580-9. PMID: 22146342.
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    10. Cecchini S, Virag T, Kotin RM. Reproducible high yields of recombinant adeno-associated virus produced using invertebrate cells in 0.02- to 200-liter cultures. Hum Gene Ther. 2011 Aug; 22(8):1021-30. PMID: 21381980.
      View in: PubMed
    11. Kotin RM. Large-scale recombinant adeno-associated virus production. Hum Mol Genet. 2011 Apr 15; 20(R1):R2-6. PMID: 21531790.
      View in: PubMed
    12. Virag T, Cecchini S, Kotin RM. Producing recombinant adeno-associated virus in foster cells: overcoming production limitations using a baculovirus-insect cell expression strategy. Hum Gene Ther. 2009 Aug; 20(8):807-17. PMID: 19604040.
      View in: PubMed
    13. Smith RH, Levy JR, Kotin RM. A simplified baculovirus-AAV expression vector system coupled with one-step affinity purification yields high-titer rAAV stocks from insect cells. Mol Ther. 2009 Nov; 17(11):1888-96. PMID: 19532142.
      View in: PubMed
    14. Cecchini S, Negrete A, Virag T, Graham BS, Cohen JI, Kotin RM. Evidence of prior exposure to human bocavirus as determined by a retrospective serological study of 404 serum samples from adults in the United States. Clin Vaccine Immunol. 2009 May; 16(5):597-604. PMID: 19244471.
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    15. Negrete A, Kotin RM. Strategies for manufacturing recombinant adeno-associated virus vectors for gene therapy applications exploiting baculovirus technology. Brief Funct Genomic Proteomic. 2008 Jul; 7(4):303-11. PMID: 18632744.
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    16. Hsu PY, Kotin RM, Yang YW. Glucose- and metabolically regulated hepatic insulin gene therapy for diabetes. Pharm Res. 2008 Jun; 25(6):1460-8. PMID: 18293064.
      View in: PubMed
    17. Cecchini S, Negrete A, Kotin RM. Toward exascale production of recombinant adeno-associated virus for gene transfer applications. Gene Ther. 2008 Jun; 15(11):823-30. PMID: 18401433.
      View in: PubMed
    18. Smith RH, Yang L, Kotin RM. Chromatography-based purification of adeno-associated virus. Methods Mol Biol. 2008; 434:37-54. PMID: 18470638.
      View in: PubMed
    19. Negrete A, Kotin RM. Large-scale production of recombinant adeno-associated viral vectors. Methods Mol Biol. 2008; 433:79-96. PMID: 18679618.
      View in: PubMed
    20. Negrete A, Yang LC, Mendez AF, Levy JR, Kotin RM. Economized large-scale production of high yield of rAAV for gene therapy applications exploiting baculovirus expression system. J Gene Med. 2007 Nov; 9(11):938-48. PMID: 17764098.
      View in: PubMed
    21. Szerlip NJ, Walbridge S, Yang L, Morrison PF, Degen JW, Jarrell ST, Kouri J, Kerr PB, Kotin R, Oldfield EH, Lonser RR. Real-time imaging of convection-enhanced delivery of viruses and virus-sized particles. J Neurosurg. 2007 Sep; 107(3):560-7. PMID: 17886556.
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    22. Negrete A, Esteban G, Kotin RM. Process optimization of large-scale production of recombinant adeno-associated vectors using dielectric spectroscopy. Appl Microbiol Biotechnol. 2007 Sep; 76(4):761-72. PMID: 17680241.
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    23. Negrete A, Kotin RM. Production of recombinant adeno-associated vectors using two bioreactor configurations at different scales. J Virol Methods. 2007 Nov; 145(2):155-61. PMID: 17606302.
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    24. Schirmer JM, Miyagi N, Rao VP, Ricci D, Federspiel MJ, Kotin RM, Russell SJ, McGregor CG. Recombinant adeno-associated virus vector for gene transfer to the transplanted rat heart. Transpl Int. 2007 Jun; 20(6):550-7. PMID: 17403107.
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    25. Li L, Yang L, Scudiero DA, Miller SA, Yu ZX, Stukenberg PT, Shoemaker RH, Kotin RM. Development of recombinant adeno-associated virus vectors carrying small interfering RNA (shHec1)-mediated depletion of kinetochore Hec1 protein in tumor cells. Gene Ther. 2007 May; 14(10):814-27. PMID: 17330085.
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    26. Thorsen F, Afione S, Huszthy PC, Tysnes BB, Svendsen A, Bjerkvig R, Kotin RM, Lønning PE, Hoover F. Adeno-associated virus (AAV) serotypes 2, 4 and 5 display similar transduction profiles and penetrate solid tumor tissue in models of human glioma. J Gene Med. 2006 Sep; 8(9):1131-40. PMID: 16810631.
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    27. Urabe M, Nakakura T, Xin KQ, Obara Y, Mizukami H, Kume A, Kotin RM, Ozawa K. Scalable generation of high-titer recombinant adeno-associated virus type 5 in insect cells. J Virol. 2006 Feb; 80(4):1874-85. PMID: 16439543.
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    28. Li W, Yu ZX, Kotin RM. Profiles of PrKX expression in developmental mouse embryo and human tissues. J Histochem Cytochem. 2005 Aug; 53(8):1003-9. PMID: 15879576.
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    29. Harper SQ, Staber PD, He X, Eliason SL, Martins IH, Mao Q, Yang L, Kotin RM, Paulson HL, Davidson BL. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc Natl Acad Sci U S A. 2005 Apr 19; 102(16):5820-5. PMID: 15811941.
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    30. Li L, Yang L, Kotin RM. The DNA minor groove binding agents Hoechst 33258 and 33342 enhance recombinant adeno-associated virus (rAAV) transgene expression. J Gene Med. 2005 Apr; 7(4):420-31. PMID: 15538728.
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    31. Huszthy PC, Svendsen A, Wilson JM, Kotin RM, Lønning PE, Bjerkvig R, Hoover F. 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. Hum Gene Ther. 2005 Mar; 16(3):381-92. PMID: 15812233.
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    32. Xia H, Mao Q, Eliason SL, Harper SQ, Martins IH, Orr HT, Paulson HL, Yang L, Kotin RM, Davidson BL. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat Med. 2004 Aug; 10(8):816-20. PMID: 15235598.
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    33. Hickman AB, Ronning DR, Perez ZN, Kotin RM, Dyda F. The nuclease domain of adeno-associated virus rep coordinates replication initiation using two distinct DNA recognition interfaces. Mol Cell. 2004 Feb 13; 13(3):403-14. PMID: 14967147.
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    34. Smith RH, Ding C, Kotin RM. Serum-free production and column purification of adeno-associated virus type 5. J Virol Methods. 2003 Dec; 114(2):115-24. PMID: 14625046.
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    35. Lotery AJ, Yang GS, Mullins RF, Russell SR, Schmidt M, Stone EM, Lindbloom JD, Chiorini JA, Kotin RM, Davidson BL. Adeno-associated virus type 5: transduction efficiency and cell-type specificity in the primate retina. Hum Gene Ther. 2003 Nov 20; 14(17):1663-71. PMID: 14633408.
      View in: PubMed
    36. Urabe M, Ding C, Kotin RM. Insect cells as a factory to produce adeno-associated virus type 2 vectors. Hum Gene Ther. 2002 Nov 1; 13(16):1935-43. PMID: 12427305.
      View in: PubMed
    37. Hickman AB, Ronning DR, Kotin RM, Dyda F. Structural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus Rep. Mol Cell. 2002 Aug; 10(2):327-37. PMID: 12191478.
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    38. Mastakov MY, Baer K, Symes CW, Leichtlein CB, Kotin RM, During MJ. Immunological aspects of recombinant adeno-associated virus delivery to the mammalian brain. J Virol. 2002 Aug; 76(16):8446-54. PMID: 12134047.
      View in: PubMed
    39. Yang GS, Schmidt M, Yan Z, Lindbloom JD, Harding TC, Donahue BA, Engelhardt JF, Kotin R, Davidson BL. Virus-mediated transduction of murine retina with adeno-associated virus: effects of viral capsid and genome size. J Virol. 2002 Aug; 76(15):7651-60. PMID: 12097579.
      View in: PubMed
    40. Smith RH, Afione SA, Kotin RM. Transposase-mediated construction of an integrated adeno-associated virus type 5 helper plasmid. Biotechniques. 2002 Jul; 33(1):204-6, 208, 210-1. PMID: 12139247.
      View in: PubMed
    41. Mastakov MY, Baer K, Kotin RM, During MJ. Recombinant adeno-associated virus serotypes 2- and 5-mediated gene transfer in the mammalian brain: quantitative analysis of heparin co-infusion. Mol Ther. 2002 Apr; 5(4):371-80. PMID: 11945063.
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    42. Schmidt M, Chiorini JA, Afione S, Kotin R. Adeno-associated virus type 2 Rep78 inhibition of PKA and PRKX: fine mapping and analysis of mechanism. J Virol. 2002 Feb; 76(3):1033-42. PMID: 11773379.
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    43. Yamano S, Huang LY, Ding C, Chiorini JA, Goldsmith CM, Wellner RB, Golding B, Kotin RM, Scott DE, Baum BJ. Recombinant adeno-associated virus serotype 2 vectors mediate stable interleukin 10 secretion from salivary glands into the bloodstream. Hum Gene Ther. 2002 Jan 20; 13(2):287-98. PMID: 11812284.
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    44. Ding C, Urabe M, Bergoin M, Kotin RM. Biochemical characterization of Junonia coenia densovirus nonstructural protein NS-1. J Virol. 2002 Jan; 76(1):338-45. PMID: 11739698.
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    45. Schmidt M, Afione S, Kotin RM. Adeno-associated virus type 2 Rep78 induces apoptosis through caspase activation independently of p53. J Virol. 2000 Oct; 74(20):9441-50. PMID: 11000213.
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    46. Yang YW, Kotin RM. Glucose-responsive gene delivery in pancreatic Islet cells via recombinant adeno-associated viral vectors. Pharm Res. 2000 Sep; 17(9):1056-61. PMID: 11087036.
      View in: PubMed
    47. Zabner J, Seiler M, Walters R, Kotin RM, Fulgeras W, Davidson BL, Chiorini JA. Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer. J Virol. 2000 Apr; 74(8):3852-8. PMID: 10729159.
      View in: PubMed
    48. Smith RH, Kotin RM. An adeno-associated virus (AAV) initiator protein, Rep78, catalyzes the cleavage and ligation of single-stranded AAV ori DNA. J Virol. 2000 Apr; 74(7):3122-9. PMID: 10708427.
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    49. Davidson BL, Stein CS, Heth JA, Martins I, Kotin RM, Derksen TA, Zabner J, Ghodsi A, Chiorini JA. Recombinant adeno-associated virus type 2, 4, and 5 vectors: transduction of variant cell types and regions in the mammalian central nervous system. Proc Natl Acad Sci U S A. 2000 Mar 28; 97(7):3428-32. PMID: 10688913.
      View in: PubMed
    50. Chiorini JA, Afione S, Kotin RM. Adeno-associated virus (AAV) type 5 Rep protein cleaves a unique terminal resolution site compared with other AAV serotypes. J Virol. 1999 May; 73(5):4293-8. PMID: 10196327.
      View in: PubMed
    51. Zimmermann B, Chiorini JA, Ma Y, Kotin RM, Herberg FW. PrKX is a novel catalytic subunit of the cAMP-dependent protein kinase regulated by the regulatory subunit type I. J Biol Chem. 1999 Feb 26; 274(9):5370-8. PMID: 10026146.
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    52. Chiorini JA, Kim F, Yang L, Kotin RM. Cloning and characterization of adeno-associated virus type 5. J Virol. 1999 Feb; 73(2):1309-19. PMID: 9882336.
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    53. Braddon VR, Chiorini JA, Wang S, Kotin RM, Baum BJ. Adenoassociated virus-mediated transfer of a functional water channel into salivary epithelial cells in vitro and in vivo. Hum Gene Ther. 1998 Dec 10; 9(18):2777-85. PMID: 9874275.
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    54. Chiorini JA, Zimmermann B, Yang L, Smith RH, Ahearn A, Herberg F, Kotin RM. 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. Mol Cell Biol. 1998 Oct; 18(10):5921-9. PMID: 9742109.
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    55. Smith RH, Kotin RM. The Rep52 gene product of adeno-associated virus is a DNA helicase with 3'-to-5' polarity. J Virol. 1998 Jun; 72(6):4874-81. PMID: 9573254.
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    56. 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. Recombinant adeno-associated virus for the generation of autologous, gene-modified tumor vaccines: evidence for a high transduction efficiency into primary epithelial cancer cells. Hum Gene Ther. 1998 May 1; 9(7):1049-59. PMID: 9607416.
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    57. Chiorini JA, Yang L, Liu Y, Safer B, Kotin RM. Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles. J Virol. 1997 Sep; 71(9):6823-33. PMID: 9261407.
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    58. Wendtner CM, Nolte A, Mangold E, Buhmann R, Maass G, Chiorini JA, Winnacker EL, Emmerich B, Kotin RM, Hallek M. 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. Gene Ther. 1997 Jul; 4(7):726-35. PMID: 9282174.
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    59. Smith RH, Spano AJ, Kotin RM. The Rep78 gene product of adeno-associated virus (AAV) self-associates to form a hexameric complex in the presence of AAV ori sequences. J Virol. 1997 Jun; 71(6):4461-71. PMID: 9151837.
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    60. Chiorini JA, Wiener SM, Yang L, Smith RH, Safer B, Kilcoin NP, Liu Y, Urcelay E, Kotin RM. The roles of AAV Rep proteins in gene expression and targeted integration. Curr Top Microbiol Immunol. 1996; 218:25-33. PMID: 8794243.
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    61. Chiorini JA, Wendtner CM, Urcelay E, Safer B, Hallek M, Kotin RM. High-efficiency transfer of the T cell co-stimulatory molecule B7-2 to lymphoid cells using high-titer recombinant adeno-associated virus vectors. Hum Gene Ther. 1995 Dec; 6(12):1531-41. PMID: 8664378.
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    62. Chiorini JA, Yang L, Safer B, Kotin RM. Determination of adeno-associated virus Rep68 and Rep78 binding sites by random sequence oligonucleotide selection. J Virol. 1995 Nov; 69(11):7334-8. PMID: 7474165.
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    63. Urcelay E, Ward P, Wiener SM, Safer B, Kotin RM. Asymmetric replication in vitro from a human sequence element is dependent on adeno-associated virus Rep protein. J Virol. 1995 Apr; 69(4):2038-46. PMID: 7884849.
      View in: PubMed
    64. Chiorini JA, Wiener SM, Owens RA, Kyöstió SR, Kotin RM, Safer B. Sequence requirements for stable binding and function of Rep68 on the adeno-associated virus type 2 inverted terminal repeats. J Virol. 1994 Nov; 68(11):7448-57. PMID: 7933128.
      View in: PubMed
    65. Batchu RB, Kotin RM, Hermonat PL. The regulatory rep protein of adeno-associated virus binds to sequences within the c-H-ras promoter. Cancer Lett. 1994 Oct 28; 86(1):23-31. PMID: 7954351.
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    66. Ward P, Urcelay E, Kotin R, Safer B, Berns KI. Adeno-associated virus DNA replication in vitro: activation by a maltose binding protein/Rep 68 fusion protein. J Virol. 1994 Sep; 68(9):6029-37. PMID: 8057478.
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    67. Kotin RM. Prospects for the use of adeno-associated virus as a vector for human gene therapy. Hum Gene Ther. 1994 Jul; 5(7):793-801. PMID: 7981305.
      View in: PubMed
    68. Weitzman MD, Kyöstiö SR, Kotin RM, Owens RA. Adeno-associated virus (AAV) Rep proteins mediate complex formation between AAV DNA and its integration site in human DNA. Proc Natl Acad Sci U S A. 1994 Jun 21; 91(13):5808-12. PMID: 8016070.
      View in: PubMed
    69. Chiorini JA, Weitzman MD, Owens RA, Urcelay E, Safer B, Kotin RM. Biologically active Rep proteins of adeno-associated virus type 2 produced as fusion proteins in Escherichia coli. J Virol. 1994 Feb; 68(2):797-804. PMID: 8289383.
      View in: PubMed
    70. Kotin RM, Linden RM, Berns KI. Characterization of a preferred site on human chromosome 19q for integration of adeno-associated virus DNA by non-homologous recombination. EMBO J. 1992 Dec; 11(13):5071-8. PMID: 1334463.
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    71. Kotin RM, Menninger JC, Ward DC, Berns KI. Mapping and direct visualization of a region-specific viral DNA integration site on chromosome 19q13-qter. Genomics. 1991 Jul; 10(3):831-4. PMID: 1653762.
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    72. Kotin RM, Siniscalco M, Samulski RJ, Zhu XD, Hunter L, Laughlin CA, McLaughlin S, Muzyczka N, Rocchi M, Berns KI. Site-specific integration by adeno-associated virus. Proc Natl Acad Sci U S A. 1990 Mar; 87(6):2211-5. PMID: 2156265.
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    73. Kotin RM, Berns KI. Organization of adeno-associated virus DNA in latently infected Detroit 6 cells. Virology. 1989 Jun; 170(2):460-7. PMID: 2543124.
      View in: PubMed
    74. Berns KI, Kotin RM, Labow MA. Regulation of adeno-associated virus DNA replication. Biochim Biophys Acta. 1988 Dec 20; 951(2-3):425-9. PMID: 2850017.
      View in: PubMed
    75. Fink AL, Kar D, Kotin R. Ribonuclease structure and catalysis: effects of crystalline enzyme, alcohol cryosolvents, low temperatures, and product inhibition. Biochemistry. 1987 Dec 29; 26(26):8571-9. PMID: 3442677.
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    76. Prince DL, Kotin RM, Dubin DT. Evidence that the methylation inhibitor cycloleucine causes accumulation of a discrete ribosomal RNA precursor in hamster mitochondria. Mol Biol Rep. 1986; 11(1):51-5. PMID: 3633018.
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    77. HsuChen CC, Kotin RM, Dubin DT. Sequences of the coding and flanking regions of the large ribosomal subunit RNA gene of mosquito mitochondria. Nucleic Acids Res. 1984 Oct 25; 12(20):7771-85. PMID: 6093053.
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    78. Kotin RM, Dubin DT. Sequences around the 3'-end of a ribosomal RNA gene of hamster mitochondria. Further support for the 'transcriptional attenuation' model. Biochim Biophys Acta. 1984 May 15; 782(1):106-8. PMID: 6722155.
      View in: PubMed
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