Regulation of gene expression in adeno-associated virus vectors in the brain.
Identifieur interne : 001971 ( Main/Exploration ); précédent : 001970; suivant : 001972Regulation of gene expression in adeno-associated virus vectors in the brain.
Auteurs : Rebecca P. Haberman [États-Unis] ; Thomas J. MccownSource :
- Methods (San Diego, Calif.) [ 1046-2023 ] ; 2002.
Descripteurs français
- KwdFr :
- MESH :
- génétique : Adenoviridae, Vecteurs génétiques.
- méthodes : Thérapie génétique.
- virologie : Encéphale.
- Régulation de l'expression des gènes viraux.
English descriptors
- KwdEn :
- MESH :
- genetics : Adenoviridae, Genetic Vectors.
- methods : Genetic Therapy.
- virology : Brain.
- Gene Expression Regulation, Viral.
Abstract
Regulated adeno-associated virus (AAV) vectors have broad utility in both experimental and applied gene therapy, and to date, several regulation systems have exhibited a capability to control gene expression from viral vectors over two orders of magnitude. The tetracycline responsive system has been the most used in AAV, although other regulation systems such as RU486- and rapamycin-responsive systems are reasonable options. AAV vectors influence how regulation systems function by several mechanisms, leading to increased background gene expression and restricted induction. Methods to reduce background expression continue to be explored and systems not yet tried in AAV may prove quite functional. Although regulated promoters are often assumed to exhibit ubiquitous expression, the tropism of different neuronal subtypes can be altered dramatically by changing promoters in recombinant AAV vectors. Differences in promoter-directed tropism have significant consequences for proper expression of gene products as well as the utility of dual vector regulation. Thus regulated vector systems must be carefully optimized for each application.
DOI: 10.1016/s1046-2023(02)00226-8
PubMed: 12413420
Affiliations:
- États-Unis
- Caroline du Nord
- Chapel Hill (Caroline du Nord)
- Université de Caroline du Nord à Chapel Hill
Links toward previous steps (curation, corpus...)
Le document en format XML
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The tetracycline responsive system has been the most used in AAV, although other regulation systems such as RU486- and rapamycin-responsive systems are reasonable options. AAV vectors influence how regulation systems function by several mechanisms, leading to increased background gene expression and restricted induction. Methods to reduce background expression continue to be explored and systems not yet tried in AAV may prove quite functional. Although regulated promoters are often assumed to exhibit ubiquitous expression, the tropism of different neuronal subtypes can be altered dramatically by changing promoters in recombinant AAV vectors. Differences in promoter-directed tropism have significant consequences for proper expression of gene products as well as the utility of dual vector regulation. 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The tetracycline responsive system has been the most used in AAV, although other regulation systems such as RU486- and rapamycin-responsive systems are reasonable options. AAV vectors influence how regulation systems function by several mechanisms, leading to increased background gene expression and restricted induction. Methods to reduce background expression continue to be explored and systems not yet tried in AAV may prove quite functional. Although regulated promoters are often assumed to exhibit ubiquitous expression, the tropism of different neuronal subtypes can be altered dramatically by changing promoters in recombinant AAV vectors. Differences in promoter-directed tropism have significant consequences for proper expression of gene products as well as the utility of dual vector regulation. Thus regulated vector systems must be carefully optimized for each application.</AbstractText><CopyrightInformation>Copyright 2002 Elsevier Science (USA)</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Haberman</LastName><ForeName>Rebecca P</ForeName><Initials>RP</Initials><AffiliationInfo><Affiliation>Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. rahabs@med.unc.edu</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McCown</LastName><ForeName>Thomas J</ForeName><Initials>TJ</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Methods</MedlineTA><NlmUniqueID>9426302</NlmUniqueID><ISSNLinking>1046-2023</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000256" MajorTopicYN="N">Adenoviridae</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000821" MajorTopicYN="Y">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015967" MajorTopicYN="Y">Gene Expression Regulation, Viral</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015316" MajorTopicYN="N">Genetic Therapy</DescriptorName><QualifierName UI="Q000379" MajorTopicYN="Y">methods</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005822" MajorTopicYN="N">Genetic Vectors</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading></MeshHeadingList><NumberOfReferences>45</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2002</Year><Month>11</Month><Day>5</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2003</Year><Month>4</Month><Day>24</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2002</Year><Month>11</Month><Day>5</Day><Hour>4</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">12413420</ArticleId><ArticleId IdType="pii">S1046202302002268</ArticleId><ArticleId IdType="doi">10.1016/s1046-2023(02)00226-8</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li></region><settlement><li>Chapel Hill (Caroline du Nord)</li></settlement><orgName><li>Université de Caroline du Nord à Chapel Hill</li></orgName></list><tree><noCountry><name sortKey="Mccown, Thomas J" sort="Mccown, Thomas J" uniqKey="Mccown T" first="Thomas J" last="Mccown">Thomas J. 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