Selected Published Works of Dr. Paul Hermonat, PhD

Unpublished Research from Dr. Paul Hermonat, PhD.

Available for download here, this historic paper was submitted in 1984 for the University of Florida Research Competition. This was the first “paper” written on AAV’s first use as a gene therapy vector. While unpublished, it was distributed, and won 1st place in the competition:

“Use of Adeno-Associated Virus as a Mammalian Transducing Vector: Transformation of Human and Murine Cells to G-418 Resistance”

Genetic and Molecular Biology of AAV

a. Hermonat, P.L. (1984). Use of adeno-associated virus as a mammalian transducing vector: Transformation of human and murine cells to G-418 resistance. University of Florida Medical Guild, 1984, 1st Place Prize.

b. Hermonat, P.L., Labow, M.A., Wright, R., Berns, K.I., and Muzyczka, N. (1984) Genetics of adeno-associated virus: isolation and preliminary characterization of mutants in adeno-associated virus type 2. J. Virology 51(2):329-339.

c Hermonat, P.L., and Muzyczka, N. (1984) Use of adeno-associated virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue culture cells. Proc. Natl. Acad. Sci. U.S.A. 81:6466-6470.

d. Hermonat, P.L. (1984). Genetic analysis and utilization of adeno-associated virus (AAV) as a mammalian cloning vector. Dissertation University Florida, 1984.

e. Labow, M.A., Hermonat, P.L., and Berns, K.I. (1986) Positive and negative autoregulation of the adeno-associated virus type 2 genome. J. Virology 60(1):251-258.

f. LaFace, D., Hermonat, P.L., Wakeland, E.K., and Peck, A.B. (1988) Gene transfer into hematopoietic progenitor cells mediated by an adeno-associated virusvector. Virology 162:483-486.

g. Batchu, R.B., Miles, D.A., Rechtin, T.M., Drake, R.R., and Hermonat, P.L. (1995) Cloning, expression and purification of full length Rep78 of adeno-associated virus as a fusion protein with maltose binding protein in Escherichia coli. Biochem. Biophy. Res. Comm. 208:714-720.

h Hermonat, P.L. (1994) Down-regulation of the human c-fos and c-myc proto-oncogene promoters by adeno-associated virus Rep78. Cancer Letters 81:129-136

i. Hermonat PL, Batchu RB. (1997) The adeno-associated virus Rep78 major regulatory protein forms multimeric complexes and the domain for this activity is contained within the carboxy half of the molecule FEBS Lett. Jan 20;401(2-3):180-4

j. Hermonat PL, Santin AD, Batchu RB. (1996) The adeno-Associated virus Rep78 major regulatory/transformation suppressor protein binds cellular Sp1 in vitro and evidence for a biological effect. Cancer Research 15;56(22): 5299-52304.

k. Bishop BM, Santin AD, Quirk JG, Hermonat PL. (1996) Role of the terminal repeat GAGC trimer, the major Rep78 binding site in adeno-associated virus DNA replication FEBS Lett. 11;397(1):97-100

l. Hermonat PL, Santin AD, Carter CA, Parham GP, Quirk JG. (1997) Multiple cellular proteins are recognized by the adeno-associated virus Rep78 major regulatory protein and the amino-half of Rep78 is required for many of these interactions. Biochem Mol Biol Int. 43(2):409-20.

m. Hermonat PL, Santin AD, Batchu RB, Zhan D. (1998) The adeno-associated virus Rep78 major regulatory protein binds the cellular TATA-binding protein in vitro and in vivo. Virology 25;245(1):120-7.

n. Hermonat PL, Quirk, J.G., Bishop, B.M., and Han, L. (1997) Packaging capacity of adeno-associated virus and the potential for wild type-plus AAV gene therapy vectors. FEBS Letters 407:78-84.

o. Meyers, C., Mane, M., Kokorina, N., Alam, S., and Hermonat, P.L. (2000) Ubiquitous adeno-associated virus type 2 replicates in a model of normal skin. Virology 272:338-346.

p. Kang BY, You H, Bandyopadhyay S, Agrawal N, Melchert RB, Basnakian AG, Liu Y, Hermonat PL. (2009) Cervical cancer isolate PT3, super-permissive for adeno-associated virus replication, over-expresses DNA polymerase delta, PCNA, RFC and RPA. BMC Microbiology. 9:79.

q. Cao M, You H, Hermonat PL. (2014) The X gene of adeno- associated virus (AAV) type 2 is involved in viral DNA replication. PLoS ONE.

r. Hermonat PL (2014) The first adeno-associated virus gene transfer experiment, 1983. Human Gene Therapy. 4: 135

s. Cao M, Bandyopadhyay S, Zhu H, You H, Hermonat PL. The HPV16 E1 carboxyl domain provide a helper function for adeno-associated virus replication. Intervirology. 2018;61(4):185-192

Cardiovascular Gene Therapy by AAV

 a. Cao M, Theus SA, Straub KD, Figueroa JA, Mirandola L, Chiriva-Internati M, Hermonat PL. AAV2/8-human Foxp3 gene therapy shows robust anti-atherosclerosis efficacy in LDLR-KO mice on high cholesterol diet.  In press J Translational Medicine, J Transl Med, 2015: 13:235.

b. Hermonat PL. Adeno-associated virus-based transgene delivery for treating progressive vascular diseases. Cloning and Transgenesis, 2014, 3:2

c. Hermonat PL, Straub KD, Chiriva-Internati M.  Improving AAV gene therapy: graduating from transgene expression “everywhere, all the time” to “disease-specific”.  Clon Transgen 3: 4, 201.

d.Zhu H, Cao M, Chriva-Internati M, Hermonat PL.  Comparison of efficacy of human interleukin 10, expressed from the disease-specific LOX1 or constitutive cytomegalovirus promoters, against atherosclerosis in mice using adeno-associated virus 2/8 delivery.  PLoS ONE, 2014: 9(4): e94665

e. Zhu H, Cao M, Figueroa JA, Cobos E, Uretsky BF, Chiriva-Internati M, Hermonat, PL.(2014) AAV2/8-hSMAD3 gene delivery attenuates aortic atherogenesis, enhances Th2 response, without inducing COL1A2/2A1 and CTGF (fibrosis) in LDLR-KO mice on high cholesterol diet. J Trans Med. 2014, 12:252

g, Zhu H, Cao M, Straub KD, Hermonat PL. Systemic delivery of thiol-specific antioxidant hPRDX6 gene by AAV2/8 inhibits atherogenesis in LDLR KO mice on HCD. Syndromes and Gene Therapy  2013, 4: 135

h.  Rhee SW, Hermonat PL, Rusch NJ.   Methods of treating hypertension.  US Patent 8227445, July 24, 2012  (AAV-based gene therapy for hypertension by delivering  BK potassium channel gene)

i. Cao M, Khan JA, Kang BY, Mehta JL, Hermonat PL.  Dual AAV/IL-10 plus STAT3 anti-inflammatory gene delivery lowers atherosclerosis in LDLR KO mice, but without increased benefit.   International Journal Vascular Medicine, 2012: 2012:524235.

j. Khan JA, Cao M, Kang B-Y, Liu Y, Mehta JL, and Hermonat PL.  Systemic hNetrin-1 gene delivery by AAV8 alters leukocyte accumulation and atherogenesis in vivo.   Gene Therapy, 2011, 18: 437-444. 

k. Hermonat PL, Zhu HQ, Cao M, Mehta JL. LOX-1 transcription. Cardiovascular Drugs and Therapy, 2011. 25: 393 Epub ahead of print.

l.  Khan JA, Cao M, Kang BY, Liu Y, Mehta JL, Hermonat PL.  AAV/hSTAT3-gene delivery lowers aortic inflammatory cell infiltration in LDLR KO mice on high cholesterol.  Atherosclerosis 2010, 213(1):59-66. 

m. Hu C, Dandapat A, Chen J, Liu Y c, Hermonat PL, Carey RM, Mehta JL.   Over-expression of angiotensin II type 2 receptor (agtr2) reduces atherogenesis and modulates LOX-1, endothelial nitric oxide synthase and heme-oxygenase-1 expression.  Atherosclerosis. 2008, 199(2):288-94.  

n. Hu C, Dandapat A, Sun L, Khan JA, Liu Y, Hermonat PL, Mehta JL. Regulation of TGFbeta1-mediated collagen formation by LOX-1: Studies based on forced overexpression of TGFbeta1 in wild-type and lox-1 knock-out mouse cardiac fibroblasts.  J. Biol. Chem. 2008, 283(16):10226-10231. 

o. Dandapat A, Hu CP, Chen J, Liu Y, Khan JA, Remeo F, Carey RM, Hermonat PL, Mehta JL.  Over-expression of angiotensin II type 2 receptor (agtr2) decreases collagen accumulation in atherosclerotic plaque.  Biochem. Biophys. Res. Commun. 2008, 366(4): 871-877.   

p. Dandapat A, Hu CP, Li D, Liu Y, Chen H, Hermonat PL, Mehta JL.  Overexpression of TGFbeta1 by adeno-associated virus type-2 vector protects myocardium from ischemia-reperfusion injury.  Gene Ther. 2008, 15(6): 415-423. 

q. Hu CP, Dandapat A, Liu Y, Hermonat PL, Mehta JL.  Blockade of hypoxia-reoxygenation-mediated collagen type 1 expression and MMP activity by overexpression of TGF-beta1 delivered by AAV in mouse cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 2007, 293(3): H1833-8. 

r. Liu, Y., Li, D., Chen; J. Xie, J., Bandyopadhyay, S., Zhang, D., Nemarkommula, A.R., Liu, H., Mehta, J.L., Hermonat, P.L. (2006)  Inhibition of atherogenesis in LDLR knockout mice by systemic delivery of adeno-associated virus type 2-hIL-10.  Atherosclerosis 188: 19-27.

Anti-Cancer Gene Therapy by AAV

a. Figueroa JA, Reidy A….Hermonat PL, Cobos E, Chiriva-Internati M. (2015) Chimeric antigen receptor engineering: A right step in adoptive cellular immunotherapy.  Internat Rev Immun 34: 154-187.

b. You CX, Shi M, Liu Y, Cao M, Luo RC, Hermonat PL.  (2012) AAV2/IL-12 gene delivery into dendritic cells (DC) enhances CTL stimulation above other IL-12 applications: evidence for IL-12 intracrine activity in DC.  Oncoimmunology  1: 847-855

c. You CX, Liu Y, Shi M, Cao M, Luo R-C, Hermonat PL.  (2010)  Comparison of AAV/IL-7 autocrine (T cell) versus paracrine (DC) gene delivery for enhancing CTL stimulation and function. Cancer Imm & Immunotherapy.  59: 779-787.

d. Zhang, D. Liu Y, Shi M, You CX, Cao M, Luo R-C, Hermonat, PL.  (2010) Autocrine, not paracrine, interferon-gamma gene delivery enhances ex vivo antigen-specific cytotoxic T lymphocyte stimulation and killing.  J. Biomed. Biotechnol. 2010: 270985

e. You, C., Liu, Y., Luo, R., You, H. Hermonat, P.L., and Mahadevan, M. (2007) Immunotherapy using cytotoxic T lymphocytes against PSMA for prostate cancer. Book chapter in Cancer and Gene Therapy, Research Signpost, Kerala, India, pg 155-168.

f. Mahadevan M, Liu Y, You C,… Hermonat, P.L., (2007) Generation of robust cytotoxic T lymphocytes against prostate specific antigen by transduction of dendritic cells using protein and recombinant adeno-associated virus. Cancer Immunol Immunother 56:1615-24, 2007

g. Prasad, C.K., Liu, Y., You, C., Luo, R., Mehta, J.L. and Hermonat, P.L. (2007) Generation, comparison of cytotoxic T lymphocyte stimulation against Her2/neu by rAAV and protein antigen loading of dendritic cells.  Book chapter in Cancer and Gene Therapy, Research Signpost, Kerala, India, Hermonat, Paul L. Editor pp 17-28.

h. You, H., Liu, Y., Cong, M., You, CX, Mehta, J.L., Hermonat, P.L.  (2006)  HBV genes induce cytotoxic T lymphocyte response upon adeno-associated virus (AAV) vector delivery into dendritic cells.  J. Viral Hepatitis 13: 605-612.

i. Liu, Y., Zhou, W., You, C., Zheng, H. You, H.,….and Hermonat, P.L.  (2006)  An autoimmune-depleted HCV core gene gives cytotoxic T cell response upon AAV vector delivery into dendritic cells.  Vaccine 24:1615-1624.

j. Chiriva-Internati M, Liu Y, … Hermonat, P.L. Testing recombinant adeno-associated virus-gene loading of dendritic cells for generating potent cytotoxic T lymphocytes against a prototype self-antigen, multiple myeloma HM1.24. Blood 102:3100-7, 2003

k. Liu Y,…Hermonat PL.  (2001) Rapid induction of cytotoxic T-cell response against cervical cancer cells by human papillomavirus type 16 E6 antigen gene delivery into human dendritic cells by an adeno-associated virus vector.  Cancer Gene Ther 8: 948-957.

l. Liu Y, Santin AD, Mane M, Chiriva-Internati M, Parham GP, Ravaggi A, Hermonat PL. Transduction and utility of granulocyte-macrophage colony-stimulating factor gene into monocytes and dendritic cells by adeno-associated virus. J Interferon Cytokine Res. 2000 Jan;20(1):21-30.

m. Liu Y, Chiriva-Internati M, You CX, Luo R, You H, Prasad CK, Grizzi F, Cobos E, Klimberg VS, Kay H. Mehta JL, Hermonat PL. Use and specificity of breast cancer/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells. Cancer Gene Therapy, 12: 304-312.