Subject Index

a-glucosidase 172 a-synuclein 130 a1-antitrypsin promoter 51 AAV 25-26,31,36-37, 119,121,

166 - long-term transgene expression

121 - production 26 - safety 37 - serotypes 31 - site-specific integration 121 - vectors 25 - crystal structure 36 AAV1 32 AAV2 32 AAV3 32 AAV5 33 AAV6 32 Acetylcholine 128 Ad5-FGF4 61--63, 66-68, 70,

72-76 - chronic efficacy study 66 - clinical results 68 - dose-response study 66 - evidence of clinical efficacy 73 - evidence of therapeutic efficacy

74 - first-pass cardiac uptake 70 - intracoronary administration 61 - in pigs 63 - long-term safety 72

- Phase III trial 76 - stabilization in RPDS 75 - toxicology and biodistribution 67 adena-associated virus

(AAV) 4,166, 225 adena-associated virus type 2

(AAV2) 25 adenosine SPECT imaging 68 adenosine stress test 74 adenoviral vectors 3, 36 - replication-defective 3 - retargeting 36 adenovirus 46,62,96-97,

107-112, 119-120 - immunogenicity 120 - intravascular delivery of 46 - retargeting and systemic delivery

107-112 - vectors 119 Ad-free system 26 adult HSCs 211 AGENT trial 21-22,68,71-75 AGENT-II trial 68, 71-72, 74-75 albumin promoter 51 ALS 127, 137, 139-140, 192 Alzheimer's disease 126-127 amyotrophic lateral sclerosis 137 angiogenesis 5, 20, 62 angiogenesis clinical trials 19 Angiogenic GENe Therapy

(AGENT) trial 68

246

angiogenic therapy 22 - clinical trials 22 angioplasty 69 animal models 168 anti-Ad5 antibody 71, 75 anticoagulants 219, 220 antigen-specific immune response

51 antiprogestin-controllable transgene

expression 229-233, 236--241 anti-sense RNAs 198 apolipoprotein E (ApoE) 128, 225 apoptosis 133, 136, 139 apoptotic pathway 200 APP 129 aptamer 9.3t 221 APTitime 35 arteriogenesis 20 artificial gene deli very system 41 atherosclerosis 72 - acceleration of 72 autosomal dominant mutation 133

P-amyloid 127 P-amyloid plaques 129 B7-l (CD80) 82 B7-2 (CD86) 82 bacterial repressor proteins 227 - P-galactoside-dependent systems

227 - streptogramin-dependent systems

227 - tetracycline-dependent systems

227 bad 139 BALB/c mice 34 basic fibroblast growth factor

(bFGF) 5 bax 139 bcl-2 136, 139 bcl-2 gene 200 BDNF 132, 136, 140

Subject Index

Becker muscular dystrophy 172 bile duct 46 blocking limb blood flow 50 blood pressure cuff 50 blood-brain barrier 161 BMD 172 bone marrow (BM) transplantation

212 Buerger's disease 54 bypass graft 70 bypass graft failure 7

CABG 69 calcineurin 8 calmodulin 8 cancer immunotherapy 82-86 cancer screening 72 capsid (cap) gene 25, 121 CAR 37, 108, 110-111 cardiac muscle 50 cardiovascular disease 5 - gene therapy for 5 cationic lipid 125 CD34 211 CD95 83 CD95(Fas)-CD95 ligand (CD95l,

Apol-ligand, Fas ligand) 82 CD95+ 83 CD95-CD95L 84 CD95L 82-83, 85 cell-cycle inhibitors 7 cell-mediated immune responses

26 chemokine receptor 5 (CCR5) 10 chicken P-actin promoter 164 choline 128 choline acetyl transferase

(ChAT) 129 chromosome 19 26, 127 chronic myocardial ischemia 6, 62 - ameroid model in pig 62 chronic stable angina 68

Subject Index

circulating FGF4 70 CK-MB 66 clinical-grade production 27 CMV promoter 53, 164 CNS 125, 161 CNS diseases 117, 159 CNS gene therapy 117 CNTF 132, 136, 140 collateral blood vessels 53 collateral perfusion 62 collateral vessels 19 complementary oligonucleotides

218 coronary artery disease 6, 61 Coxsackie and Adenovirus Recep-

tor (CAR) 70, 107 CpG methylation 51 CPK 66 ere recombinase 198 CSF 197

decoys 217 Del-l 20 dementia 130, 133 diabetes 69 DMD 163,170 DNA nuclear uptake 53 dog 49 dopamine 130, 193-194 dopaminergic neurons 130 drug-coated stents 8 drug-dependent gene expression

systems 226-233, 236-240 drug-regulated systems for in vivo

gene transfer studies 228 Duchene muscular dystrophy 49,

163 dystrophin 163, 168, 170 dystrophin gene 168

247

E2F 7,218 E2F-targeted decoy oligonucleotides

7 endothelium-specific promoter 212 EIAV 180-183, 185, 195 - regions 181 - vector 183, 195 electroporation 42 electroporation of plasmid

234-236 endothelial barrier 52 endothelial progenitor cells 211 env gene 125, 180, 184 EPCs 211 equine infectious anaemia virus

180 ETT 73 ex vivo gene delivery 126 examples of replication-selective

viruses in clinical trials 90-92 - adenovirus 90, 92 - autonomous parvoviruses 91, 93 - herpes simplex virus-1 90, 92 - measles 92 - newcastle disease virus 91-92 - reovirus 91-92 - vaccinia virus 90 exercise treadmill testing (ETT) 68 extracellular matrix 7

factoriX 27,47,218,220, 225-226

factor IXa aptamer 219 factor VIII 4 7 familial spastic paraplegia 137 feline immunodeficiency virus 125 fenestrae 52 FGF-4 gene delivery 22 FGF-4 mRNA 68 FGF-5 62 fibroblast growth factor (FGF) 20,

61

248

fibrosis 66 FIRST trial 21-22 first-generation Ad vectors 120 FIV 125, 182 Flk-1 211-212 FSP 137

gag genes 125, 180, 184 gag-polgenes 202 Gaucher's disease 171, 197 GDNF 132, 136, 140, 196 gene gun 42 gene knockout 138 gene replacement 163, 170 gene therapy 2 - vectors for 2 gene transfer 189 GeneSwitch 236-240 genetic vaccines 51 GH loop 36 glial cells 129 glioblastoma 72 granulocyte macrophage-colony

stimulating factor (GM-CSF) 20,212

green fluorescence protein (GFP) 33

"gutted" adenovirus 166

HAP-I 134 HD 133, 136 HD gene 134 heart failure 69 heart ischemia 50 helper plasmid 26 helper-dependent (gutless) ade-

novirus vectors 120, 225 hemagglutinating virus of Japan

(HVJ) 8 hematopoietic stem cells 211 hemophilia B dogs 28 hemophilia B gene therapy 30,33

heparan sulfate 36 hepatitis C 71

Subject Index

Herpes Simplex virus vectors 122 heterodimeric proteins 227 HI loop 36 hind limb ischemia 6 HIP-I, -2 135 histone deacetylases (HDACs) 8 HIV 10, 185 HIV-1 125, 180-182 - coding regions 181 HIV-2 180 HLA-B7 DNA 82 HSC 211 HSV 96, 99-100, 119 HSV amplicon vectors 123 HSV amplicon, helper-free packag-

ing system 123 HSV-1 122 HSV-Tk 198 human immunodeficiency virus

125, 180 huntingtin 134-135 Huntington's disease 127, 130,

133 hurdles to virotherapy 97-98 - clearance of viruses from the

bloodstream 98 - complement-mediated clear­

ance 97 - neutralizing antibodies 97 hydrodynamic delivery 47

ICP4 122 IGF-1 140, 172 infectious diseases 10 insertional mutagenesis 37 in-stent restenosis 8 integration 124 intravascular delivery to limb skele­

tal muscle 49 inverted terminal repeats (ITRs) 25

Subject Index

ischemia 215 ischemic ulcers 53

Jat 180

Kupffer cells 112

L-arginine 8 L-dopa therapy 131, 195-196 1entiviral vector 3, 119, 125, 179,

182,199,226 - safety of 99 Lewy bodies 130 LIF 140 lipoplexes 42 liposomes 8 liver enzymes 66 Lou Gehrig's disease 192 LTR 183 luciferase 47

major histocompatibility complex (MHC) class I protein 82

- HLA-B7-1 (CD80) 82 - HLA-B7-2 (CD86) 82 MAO-B 131 MCK promoter 164 MCP-1 20 mdx mouse 168 measles 97-99 measles vaccine strain (MV -SPUD)

98 mechanisms of tumor selective repli-

cation 93-95 - adenovirus 93-94 - autonomous parvoviruses 93-95 - herpes simplex virus-1 93-94 - new castle disease virus 93, 95 - poliovirus 93 - reovirus 93, 95 - vaccinia virus 93 - vsv 93,95

249

metastatic colon cancer 72 MND 192 monomethoxypolyethylene glycol

(PEG) 108 motor neuron disease 117, 137,

189, 192 - models of 137 MPTP 131, 194 murine CMV enhancer 164 muscle gene delivery 27 myoblasts 140 myocardial gene therapy 62 myocardial gene transfer 70 myocardial infarction 9, 214 myocardial inflammation 62 myocardial ischaemia 19, 22, 62 myocardial oxygen demand 63 myocardium 4 myocyte enhancer factor-2 (MEF-2)

8

naked DNA 45, 53, 125 - direct injection of into muscle 45 - in clinical studies for P AOD 53 - intra-muscular injection 53 neointimal hyperplasia 8 neovascularization 5, 71 nerve growth factor 129 neural stem cells 132 neurites 189 neuritic plaques 127 neurodegenerati ve diseases 117,

127, 137, 139 neurofibrillary tangles 137 neurological disease 179 neuron disorders 137 neuronal transduction 187 neuron-specific promoters 164 neuroprotection 131-132 neuroregeneration 131 neurotropic virus 122 neurotrophic factors 140

250

neutralizing antibodies 30, 97 NGF 129, 140 nitric oxide (NO) 8 nitric oxide synthase 7, 139 - inhibitors 139 NMDA receptors 138 NOD/SCID mice 33 non-dividing cells 182 nonviral vectors 4, 41, 43, 165 - for cardiovascular gene delivery

41 - potential advantages of 43 NTN 132 nuclear hormone receptors 227,

233 - antiprogestin-dependent system

227 - antiestrogen-dependent system

227 - secreted alkaline phosphatase

(SEAP) 233 - erythropoietin (EPO) 233 - vascular endothelial growth fac-

tor (VEGF) 233 - growth hormone releasing hor­

mone (GHRH) 233 - ecdysteroid-dependent system

227 - glucocorticoid-dependent system

227

oncolytic virotherapy 92 oxidative damage 133, 139 oxidative stress 135, 139

Parkinson's disease 117, 127, 130, 193

parvovirus 25 PCR 68 PD 193 pDNA vector 52 - CpG content of 52

Subject Index

peripheral arterial occlusion disease (PAOD) 53

peripheral vascular disease 19, 22 pig model of myocardial ischemia

63 plaque angiogenesis 72 plaque rupture 9 plasmid DNA 4, 45-47 - intravascular delivery of 46 - rapid injection of 47 - use of electroporation 45 plasmid-based gene transfer

225-228,234-236 platelet-derived growth factor

(PDGF) 61 pol 184 pol genes 125,180 Poly[N-(2-hydroxypropyl)methacry-

lamide] (PHPMA) 108-110, 112

polyplexes 42

51, 166

Pompe's disease 171 portal vein 46 presenilins 129 progenitor cells 211 promoter inactivation ProSavin 194 proteasome 134 pseudotyped EIA V pseudotyped vectors pseudotyping 186

186 191

rAAV 26 - packaging technology 26 rAAV2 27,30 - bio-distribution of 30 rabbit 49 rabies-G 186, 190, 197 - EIA V vectors 197 - envelope 186 RAR-~2 189, 191 Rb-G vectors 191

Subject Index

recombinant FGF-2 protein 22 recombinant VEGF protein 22 - for the treatment of coronary

heart disease 22 recombination 199 replication (rep) gene 25, 121 replication-competent lenti-virus

199 retargeting agents 109-110 - bFGF 109 - FGF2 109 - SIGYPLP 110 - VEGF 109 retinoic acid receptor 189 retinopathy 22, 69 retrograde delivery 50 retrograde transport 186 retroviral vectors 3, 124 retroviruses 180 Rev 184,218 Rev protein 182 rhesus monkey 50 RNA interference (RNAi) 54 RNA viruses 180 RT-PCR 68

Saf 199 SELEX 218 semen 70 serotype domain swaps 37 shear stress 20 short interfering RNAs (siRNAs)

9,54,198 site-directed mutagenesis 37 SIV 182 skeletal muscle 27 skeletal muscle diseases 159, 163 skeletal muscle fibers 162 Sly syndrome 197 SOD-1 138 somatic gene therapy 27 SPECT sestamibi 74

spinal cord 189 spinal injuries 189 spinal muscular atropy 137 stem cells 211 stroke 9 substantia nigra 130

251

superoxide dismutase 133 sustained expression of trans genes

50 synthetic vectors 43

tail vein delivery 47 TAR 182 Tat 182,220 Tay-Sachs disease 197 T-cells 10 tetracycline-regulated promoter

183 TGF-~ 84-85 TH promoter 124 TH+ neurons 196 therapeutic angiogenesis 5, 19-20 - mechanisms of 20 therapeutic aptamers 217 thrombosis 220 Tie-2 212 tourniquet 50 TRAFFIC trial 21-22 transaminase elevations 71 transgenic mice 137-139 transplant atherosclerosis 9 tumor-infiltrating lymphocytes

(TILs) 82 tumor-specific plasmid DNA

(pDNA) vaccine 85 tyrosine hydroxylase 123

ubiquitin/proteasome pathway 134 unstable angina 69 utrophin 170

252

vaccinia 96, 98-99 vascular endothelial growth factor

(VEGF) 5, 20, 61 vascular proliferative disorders 7 vascular smooth muscle 7 vasculogenesis 211, 213 VEGF 54 VEGFm 6 VEGFJ65 6 VEGF2 7 viral DNA 68

viral tropism 119 viral vectors 2, 43 virus type l 125 VIVA trial 21-22

Subject Index

VSV-G envelope 183-184, 186 VSV-G pseudotyped vectors 188

wall thickening 63 - in the ischemic region 63 wild-type AA V 26 WPRE 184

Ernst Schering Research Foundation Workshop

Editors: Gunter Stock Monika Lessl

Vol. 1 (1991): Bioscience'=; Society- Workshop Report Editors: D. J. Roy, B. E. Wynne, R. W. Old

Vol. 2 (1991): Round Table Discussion on Bioscience'=7Society Editor: J. J. Cherfas

Vol. 3 (1991): Excitatory Amino Acids and Second Messenger Systems Editors: V. I. Teichberg, L. Turski

Vol. 4 (1992): Spermatogenesis- Fertilization- Contraception Editors: E. Nieschlag, U.-F. Habenicht

Vol. 5 (1992): Sex Steroids and the Cardiovascular System Editors: P. Ramwell, G. Rubanyi, E. Schillinger

Vol. 6 (1993): Transgenic Animals as Model Systems for Human Diseases Editors: E. F. Wagner, F. Theuring

Vol. 7 (1993): Basic Mechanisms Controlling Term and Preterm Birth Editors: K. Chwalisz, R. E. Garfield

Vol. 8 (1994): Health Care 2010 Editors: C. Bezold, K. Knabner

Vol. 9 (1994): Sex Steroids and Bone Editors: R. Ziegler, J. Pfeilschifter, M. Brautigam

Vol. 10 (1994): Nongenotoxic Carcinogenesis Editors: A. Cockburn, L. Smith

Vol. 11 (1994): Cell Culture in Pharmaceutical Research Editors: N. E. Fusenig, H. Graf

Vol. 12 (1994): Interactions Between Adjuvants, Agrochemical and Target Organisms Editors: P. J. Holloway, R. T. Rees, D. Stock

Vol. 13 (1994): Assessment of the Use of Single Cytochrome P450 Enzymes in Drug Research Editors: M. R. Waterman, M. Hildebrand

Vol. 14 (1995): Apoptosis in Hormone-Dependent Cancers Editors: M. Tenniswood, H. Michna

Vol. 15 (1995): Computer Aided Drug Design in Industrial Research Editors: E. C. Herrmann, R. Franke

Vol. 16 {1995): Organ-Selective Actions of Steroid Hormones Editors: D. T. Baird, G. Schlitz, R. Krattenmacher

Vol. 17 (1996): Alzheimer's Disease Editors: J.D. Turner, K. Beyreuther, F. Theuring

Vol. 18 (1997): The Endometrium as a Target for Contraception Editors: H.M. Beier, M.J.K. Harper, K. Chwalisz

Vol. 19 (1997): EGF Receptor in Tumor Growth and Progression Editors: R. B. Lichtner, R. N. Harkins

Vol. 20 {1997): Cellular Therapy Editors: H. Wekerle, H. Graf, J.D. Turner

Vol. 21 (1997): Nitric Oxide, Cytochromes P 450, and Sexual Steroid Hormones Editors: J.R. Lancaster, J.F. Parkinson

Vol. 22 (1997): Impact of Molecular Biology and New Technical Developments in Diagnostic Imaging Editors: W. Semmler, M. Schwaiger

Vol. 23 (1998): Excitatory Amino Acids Editors: P.H. Seaburg, I. Bresink, L. Turski

Vol. 24 (1998): Molecular Basis of Sex Hormone Receptor Function Editors: H. Gronemeyer, U. Fuhrmann, K. Parczyk

Vol. 25 {1998): Novel Approaches to Treatment of Osteoporosis Editors: R.G.G. Russell, T.M. Skerry, U. Kollenkirchen

Vol. 26 (1998): Recent Trends in Molecular Recognition Editors: F. Diederich, H. KOnzer

Vol. 27 (1998): Gene Therapy Editors: R.E. Sobol, K.J. Scanlon, E. Nestaas, T. Strohmeyer

Vol. 28 (1999): Therapeutic Angiogenesis Editors: J.A. Dormandy, W.P. Dole, G.M. Rubanyi

Vol. 29 (2000): Of Fish, Fly, Worm and Man Editors: C. NOsslein-Volhard, J. Kratzschmar

Vol. 30 (2000): Therapeutic Vaccination Therapy Editors: P. Walden, W. Sterry, H. Hennekes

Vol. 31 (2000): Advances in Eicosanoid Research Editors: C.N. Serhan, H.D. Perez

Vol. 32 (2000): The Role of Natural Products in Drug Discovery Editors: J. Mulzer, R. Bohlmann

Vol. 33 (2001): Stem Cells from Cord Blood, In Utero Stem Cell Development, and Transplantation-Inclusive Gene Therapy Editors: W. Holzgreve, M. Lessl

Vol. 34 (2001): Data Mining in Structural Biology Editors: I. Schlichting, U. Egner

Vol. 35 (2002): Stem Cell Transplantation and Tissue Engineering Editors: A. Haverich, H. Graf

Vol. 36 (2002): The Human Genome Editors: A. Rosenthal, L. Vakalopoulou

Vol. 37 (2002): Pharmacokinetic Challenges in Drug Discovery Editors: 0. Pelkonen, A. Baumann, A. Reichel

Vol. 38 (2002): Bioinformatics and Genome Analysis Editors: H.-W. Mewes, B. Weiss, H. Seidel

Vol. 39 (2002): Neuroinflammation - From Bench to Bedside Editors: H. Kettenmann, G. A. Burton, U. Moenning

Vol. 40 (2002): Recent Advances in Glucocorticoid Receptor Action Editors: A. Cato, H. Schaecke, K. Asadullah

Vol. 41 (2002): The Future of the Oocyte Editors: J. Eppig, C. Hegele-Hartung

Vol. 42 (2003): Small Molecule- Protein Interaction Editors: H. Waldmann, M. Koppitz

Vol. 43 (2003): Human Gene Therapy: Present Opportunities and Future Trends Editors: G. M. Rubanyi, S. Yla-Herttuala

Supplement 1 (1994): Molecular and Cellular Endocrinology of the Testis Editors: G. Verhoeven, U.-F. Habenicht

Supplement 2 (1997): Signal Transduction in Testicular Cells Editors: V. Hansson, F. 0. Levy, K. Tasken

Supplement 3 (1998): Testicular Function: From Gene Expression to Genetic Manipulation Editors: M. Stefanini, C. Boitani, M. Galdieri, R. Geremia, F. Palombi

Supplement 4 (2000): Hormone Replacement Therapy and Osteoporosis Editors: J. Kato, H. Minaguchi, Y. Nishino

Supplement 5 (1999): Interferon: The Dawn of Recombinant Protein Drugs Editors: J. Lindenmann, W.O. Schleuning

Supplement 6 (2000): Testis, Epididymis and Technologies in the Year 2000 Editors: B. Jegou, C. Pineau, J. Saez

Supplement 7 (2001): New Concepts in Pathology and Treatment of Autoimmune Disorders Editors: P. Pozzilli, C. Pozzilli, J.-F. Kapp

Supplement 8 (2001): New Pharmacological Approaches to Reproductive Health and Healthy Ageing Editors: W.-K. Raft, M. F. Fathalla, F. Saad

Supplement 9 (2002): Testicular Tangrams Editors: F.F.G. Rommerts, K.J. Teerds

Supplement 10 (2002): Die Architektur des Lebens Editors: G. Stock, M. Lessl