Antisense technology in the central nervous system:
Saved in:
| Format: | Book |
|---|---|
| Language: | English |
| Published: |
Oxford
Oxford Univ. Press
1999
|
| Edition: | 1. publ. |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Physical Description: | XVII, 250 S. zahlr. Ill. |
| ISBN: | 0198503164 |
Staff View
MARC
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| 245 | 1 | 0 | |a Antisense technology in the central nervous system |c ed. by Ronald A. Leslie ... |
| 250 | |a 1. publ. | ||
| 264 | 1 | |a Oxford |b Oxford Univ. Press |c 1999 | |
| 300 | |a XVII, 250 S. |b zahlr. Ill. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 4 | |a Antisense nucleic acids | |
| 650 | 4 | |a Central Nervous System | |
| 650 | 4 | |a Gene Expression Regulation | |
| 650 | 4 | |a Genetic regulation | |
| 650 | 4 | |a Neurogenetics | |
| 650 | 4 | |a Oligonucleotides, Antisense | |
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Record in the Search Index
| _version_ | 1804128127297781760 |
|---|---|
| adam_text | Contents
List of con trib u tors xv
Abbreviations xix
1. Antisense oligonucleotide regulation of gene
expression in the CNS: an overview 1
R. A. Leslie, A. J. Hunter and H. A. Robertson
1. Introduction 1
2. The theory of antisense gene knockdown and design of
synthetic antisense molecules 2
3. Advantages and disadvantages of the technique—comparison
with transgenics 3
4. Uptake of antisense ODNs by experimental cells and tissues
and the issue of controls 4
5. Antisense oligodeoxynucleotide delivery systems 5
6. Alternative gene knockdown technologies 6
References 7
2. Antisense knockdown in the CNS—optimizing
the strategy 8
Siew Peng Ho and Paul R. Hartig
1. Introduction 8
2. Selection of potent oligonucleotide sequences for the antisense
experiment 8
3. Tissue culture experiments 9
4. Selecting parameters for the in vivo experiment 10
5. Cellular localization of ODNs in vivo 11
6. Controls 13
7. Mechanisms of antisense knockdown in the brain 13
8. Selection of chemical analogs for in vivo antisense
experiments 15
9. Biochemical evidence for antisense effects—increasing
protein and RNA knockdown 16
Contents
10. Summary 17
References 18
3. The design of appropriate control
experiments to ensure specificity in antisense
oligonucleotide function 21
Wolfgang Brysch
1. Introduction 21
2. Effects of antisense oligodeoxynucleotides 21
2.1 Sequence specific effects 21
2.2 Sequence related side effects 22
2.3 Substance related effects 24
3. Controls 24
3.1 Sense controls 25
3.2 Random controls 26
3.3 Reverse controls 29
3.4 Mismatch controls 30
3.5 Non expressing control cells 31
3.6 Second antisense 32
4. Assay systems 33
4.1 Measurement of target mRNA levels: Northern blots and RT PCR 33
4.2 Measurement of protein levels 34
4.3 Biochemical assays 36
4.4 Binding assays 37
4.5 Cell proliferation 38
4.6 Morphological analysis 38
4.7 Functional assays 40
References 40
4. Modulation of gene expression in the CNS as
a tool in behavioral pharmacology 42
Wolfgang Sommer and Markus Heilig
1. Introduction 42
2. Functional analysis of G protein coupled receptors 42
2.1 The Yl subtype of NPY receptors 42
2.2 The dopamine D2 receptor family: different roles of D2 and D3
subtypes 43
2.3 Practical considerations in the antisense suppression of G protein
coupled receptors 45
viii
Contents
3. Functional role of c fos in the adult CNS 47
3.1 Antisense blockade of c fos expression in selected regions of the brain 47
4. Pharmacokinetics of oligonucleotides in the brain 52
5. Summary and perspectives 60
References 60
5. Behavioral and neuroendocrine effects of
antisense targeting in the rat 64
R. Landgraf
1. Introduction 64
2. Methodological considerations 65
2.1 Controls 65
2.2 Homology 66
2.3 Specificity 67
2.4 Administration 70
3. Antisense effects on behavioral and neuroendocrine
regulation 73
References 78
6. Electrophysiological and behavioral effects of
dopamine receptor knockdown in the brain si
Simranjit Kaur, Ian Creese and James M. Tepper
1. Introduction 81
2. Antisense technology applied to dopamine receptor research 82
2.1 Spread of D2 receptor antisense oligodeoxynucleotides in the brain 84
3. Electrophysiological consequences of antisense knockdown 85
3.1 Antisense knockdown of presynaptic D2 receptors 85
3.2 Antisense knockdown of D3 autoreceptors 86
4. Behavioral consequences of antisense knockdown of
dopamine receptors 89
4.1 Antisense knockdown of dopamine Dt receptors 89
4.2 Antisense knockdown of dopamine D2 receptors 89
4.3 Antisense knockdown of dopamine D3 receptors 90
5. The effects of D2 receptor knockdown on tyrosine hydroxylase
expression in substantia nigra 91
6. Conclusions 93
Acknowledgements 93
References 93
ix
Contents
7. Antisense mapping: exploring the functional
significance of alternative splicing 98
Gavril W. Pasternak
1. Introduction 98
2. Antisense mapping of DOR 1, a delta opioid receptor 98
3. Antisense mapping of MOR 1, a mu opioid receptor 99
4. Antisense mapping of neuronal nitric oxide synthase 101
5. Conclusion 105
References 105
8. Medicinal chemistry of antisense
oligonucleotides ios
Sudhir Agrawal and Ekambar R. Kandimalla
1. Introduction 108
2. Desirable properties of effective antisense oligonucleotides 108
3. Choice of chemical modifications 109
4. PS ONs 110
4.1 Synthesis 112
4.2 Purification 112
4.3 Characterization 113
4.4 Radiolabeling 113
5. Factors that influence antisense activity 113
5.1 Target site 113
5.2 Base composition and sequence of antisense oligonucleotide 114
5.3 Delivery of oligonucleotides 117
5.4 Excretion of oligonucleotides 118
5.5 Safety of PS ONs 119
6. Beyond phosphorothioate oligonucleotides 121
7. Mixed backbone oligonucleotides 121
7.1 End modified MBOs 123
7.2 Centrally modified MBOs 126
8. Oral and colorectal delivery of MBOs 127
9. Other important modifications 128
9.1 Oligonucleotides containing a 3 hairpin structure or self stabilized
oligonucleotides 128
9.2 3 3 Linked oligonucleotides 128
9.3 Pro or bio reversible oligonucleotide analogs 129
9.4 Stereoregular PS ONs 129
x
Contents
10. Conclusions and future perspectives 129
References 131
9. Retinal neuronal development in trkB
antisense knockdowns 137
Dennis W. Rickman
1. Introduction 137
2. Neuronal differentiation in the rodent retina 139
3. Antisense oligonucleotides in suppression of retinal proteins 140
4. Design of a specific antisense oligonucleotide targeted to the
fricBmRNA 141
4.1 Delivery of oligonucleotides to the eye 142
4.2 Suppression of TrkB expression in the retina 142
4.3 Effects on a retinal neuronal phenotype 143
5. Summary of results 146
5.1 Knockdowns versus knockouts 146
5.2 Targeting to the retina 146
5.3 Interpretation of results 147
Acknowledgements 147
References 147
10. Pluronic gel as a means of antisense delivery 149
David L. Becker, Jun Sheng Lin and Colin R. Green
1. Introduction 149
2. Methods 150
2.1 Pluronic gel and antisense preparation 150
2.2 Pluronic gel application to chick embryos in ovo 151
2.3 Application of Pluronic gel plugs into rat brain lesions 152
3. Tips for a successful experiment 154
Acknowledgements 157
References 157
11. Delivery of antisense by viral vectors for
prolonged antisense effects in vivo iss
M. Ian Phillips, Xiaoping Tang and Dagmara Mohuczy
1. Introduction 158
xi
Contents
2. Antisense oligonucleotides 159
2.1 Designing antisense molecules 159
2.2 Stability of oligonucleotides 161
2.3 Cellular uptake of oligonucleotides 162
2.4 Pharmacology of antisense ODNs 162
2.5 Toxicity 163
2.6 Delivery of antisense 163
3. Viral vectors for antisense DNA delivery 164
3.1 Retroviruses 165
3.2 Adenoviruses 165
3.3 Adeno associated virus 166
4. Methods for antisense delivery by AAV 167
4.1 Construction of plasmids 167
4.2 Preparation of pAAV AT,R AS 172
Acknowledgements 176
References 176
12. Regulation of gene expression in the CNS by
natural antisense RNAs iso
Paul R. Murphy, Rai Knee and Audrey W. Li
1. Introduction 180
2. Evolution of antisense RNA expression 180
3. Mechanisms of natural antisense action 181
3.1 Class I antisense RNAs: regulation of mRNA processing and
translation 182
3.2 Class II antisense RNAs: regulation of mRNA stability 184
4. Does antisense RNA regulate FGF 2 expression in
mammalian tissue? 187
4.1 Detection and cloning of the mammalian FGF antisense RNA 187
4.2 Reciprocal expression of FGF 2 sense and antisense expression
in brain 189
4.3 The antisense RNA encodes a nuclear protein with antimutator
activity 191
5. Summary 192
References 192
13. Aptamers: another use for oligonucleotides 195
Richard C. Conrad
1. Introduction 195
2. Overview 196
xii
Contents
3. Starting material: the library 198
3.1 Design 199
3.2 Chemical (solid state) DNA synthesis 201
3.3 Amplification to generate a dsDNA library 203
3.4 Conversion of the initial dsDNA library to an RNA pool 205
4. Selection 206
4.1 Binding 206
4.2 Isolation of bound nucleic acids 208
5. Amplification 211
6. Termination 213
6.1 Binding assays 213
6.2 Cloning, sequencing, and structure determination 215
References 215
14. Ribozymes: oligonucleotides with enzymatic
activity have potential as regulators of gene
expression in the CNS 218
Leonidas A. Phylactou, Marc B. Lee and Matthew J. A. Wood
1. Introduction 218
2. Targeted down regulation of gene expression in the CNS
using hammerhead ribozymes 221
2.1 Design considerations 221
2.2 Construction and cell free functional assays 222
2.3 In vivo applications 223
3. Targeted RNA repair using group I intron ribozymes 224
3.1 Design considerations 225
3.2 Construction and cell free functional assays 225
3.3 In vivo applications 227
4. Conclusion 228
References 228
15. Antisense gene knockdown technology in
the nematode Caenorhabditis elegans:
applications to cholinergic synaptic
transmission 230
Emmanuel Culetto and David B. Sattelle
1. Introduction 230
xiii
Contents
2. Experimental advantages of using C. elegans for analysis of
gene function 231
2.1 A model organism for neurogenetics 231
2.2 Genetic and physical maps 232
2.3 Genome sequence 232
3. Reverse genetics 234
3.1 Tel insertion mutants 234
3.2 Chemically induced deletion mutants 235
3.3 Homologous recombination 235
4. Use of antisense technology for knockdown 235
4.1 The demonstration of antisense knockdown in C. elegans 235
4.2 Mechanism underlying antisense knockdown action involves
double stranded RNA interference 237
4.3 Possible mechanisms invoked to explain dsRNAi 238
5. Applications to neural signalling 239
5.1 Functional roles of nicotinic acetylcholine receptor gene family
members 239
5.2 Functional roles of the four acetylcholinesterase genes in
C. elegans 241
6. Conclusions 241
Acknowledgements 242
References 242
Index 245
xiv
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| spelling | Antisense technology in the central nervous system ed. by Ronald A. Leslie ... 1. publ. Oxford Oxford Univ. Press 1999 XVII, 250 S. zahlr. Ill. txt rdacontent n rdamedia nc rdacarrier Antisense nucleic acids Central Nervous System Gene Expression Regulation Genetic regulation Neurogenetics Oligonucleotides, Antisense Zentralnervensystem (DE-588)4067637-7 gnd rswk-swf Antisense-Oligonucleotide (DE-588)4371006-2 gnd rswk-swf Zentralnervensystem (DE-588)4067637-7 s Antisense-Oligonucleotide (DE-588)4371006-2 s DE-604 Leslie, Ronald A. Sonstige oth HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009105786&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Antisense technology in the central nervous system Antisense nucleic acids Central Nervous System Gene Expression Regulation Genetic regulation Neurogenetics Oligonucleotides, Antisense Zentralnervensystem (DE-588)4067637-7 gnd Antisense-Oligonucleotide (DE-588)4371006-2 gnd |
| subject_GND | (DE-588)4067637-7 (DE-588)4371006-2 |
| title | Antisense technology in the central nervous system |
| title_auth | Antisense technology in the central nervous system |
| title_exact_search | Antisense technology in the central nervous system |
| title_full | Antisense technology in the central nervous system ed. by Ronald A. Leslie ... |
| title_fullStr | Antisense technology in the central nervous system ed. by Ronald A. Leslie ... |
| title_full_unstemmed | Antisense technology in the central nervous system ed. by Ronald A. Leslie ... |
| title_short | Antisense technology in the central nervous system |
| title_sort | antisense technology in the central nervous system |
| topic | Antisense nucleic acids Central Nervous System Gene Expression Regulation Genetic regulation Neurogenetics Oligonucleotides, Antisense Zentralnervensystem (DE-588)4067637-7 gnd Antisense-Oligonucleotide (DE-588)4371006-2 gnd |
| topic_facet | Antisense nucleic acids Central Nervous System Gene Expression Regulation Genetic regulation Neurogenetics Oligonucleotides, Antisense Zentralnervensystem Antisense-Oligonucleotide |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009105786&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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