FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2017180975> ?p ?o ?g. }

• W2017180975 abstract "Gene delivery in vivo that is tightly focused on the intended target cells is essential to maximize the benefits of gene therapy and to reduce unwanted side-effects. Cell surface markers are immediately available for probing by therapeutic gene vectors and are often used to direct gene transfer with these vectors to specific target cell populations. However, it is not unusual for the choice of available extra-cellular markers to be too scarce to provide a reliable definition of the desired therapeutically relevant set of target cells. Therefore, interrogation of intra-cellular determinants of cell-specificity, such as tissue-specific transcription factors, can be vital in order to provide detailed cell-guiding information to gene vector particles. An important improvement in cell-specific gene delivery can be achieved through auto-buildup in vector homing efficiency using intelligent 'self-focusing' of swarms of vector particles on target cells. Vector self-focusing was previously suggested to rely on the release of diffusible chemo-attractants after a successful target-specific hit by 'scout' vector particles.I hypothesize that intelligent self-focusing behaviour of swarms of cell-targeted therapeutic gene vectors can be accomplished without the employment of difficult-to-use diffusible chemo-attractants, instead relying on the intra-swarm signalling through cells expressing a non-diffusible extra-cellular receptor for the gene vectors. In the proposed model, cell-guiding information is gathered by the 'scout' gene vector particles, which: (1) attach to a variety of cells via a weakly binding (low affinity) receptor; (2) successfully facilitate gene transfer into these cells; (3) query intra-cellular determinants of cell-specificity with their transgene expression control elements and (4) direct the cell-specific biosynthesis of a vector-encoded strongly binding (high affinity) cell-surface receptor. Free members of the vector swarm loaded with therapeutic cargo are then attracted to and internalized into the intended target cells via the expressed cognate strongly binding extra-cellular receptor, causing escalation of gene transfer into these cells and increasing the copy number of the therapeutic gene expression modules. Such self-focusing swarms of gene vectors can be either homogeneous, with 'scout' and 'therapeutic' members of the swarm being structurally identical, or, alternatively, heterogeneous (split), with 'scout' and 'therapeutic' members of the swarm being structurally specialized.It is hoped that the proposed self-focusing cell-targeted gene vector swarms with receptor-mediated intra-swarm signalling could be particularly effective in 'top-up' gene delivery scenarios, achieving high-level and sustained expression of therapeutic transgenes that are prone to shut-down through degradation and silencing. Crucially, in contrast to low-precision 'general location' vector guidance by diffusible chemo-attractants, ear-marking non-diffusible receptors can provide high-accuracy targeting of therapeutic vector particles to the specific cell, which has undergone a 'successful cell-specific hit' by a 'scout' vector particle. Opportunities for cell targeting could be expanded, since in the proposed model of self-focusing it could be possible to probe a broad selection of intra-cellular determinants of cell-specificity and not just to rely exclusively on extra-cellular markers of cell-specificity. By employing such self-focusing gene vectors for the improvement of cell-targeted delivery of therapeutic genes, e.g., in cancer therapy or gene addition therapy of recessive genetic diseases, it could be possible to broaden a leeway for the reduction of the vector load and, consequently, to minimize undesired vector cytotoxicity, immune reactions, and the risk of inadvertent genetic modification of germline cells in genetic treatment in vivo." @default.
• W2017180975 created "2016-06-24" @default.
• W2017180975 creator A5075523751 @default.
• W2017180975 date "2015-01-01" @default.
• W2017180975 modified "2023-09-23" @default.
• W2017180975 title "Self-focusing therapeutic gene delivery with intelligent gene vector swarms: Intra-swarm signalling through receptor transgene expression in targeted cells" @default.
• W2017180975 cites W1513552803 @default.
• W2017180975 cites W1971280003 @default.
• W2017180975 cites W1973733861 @default.
• W2017180975 cites W1982469410 @default.
• W2017180975 cites W2008332694 @default.
• W2017180975 cites W2012813333 @default.
• W2017180975 cites W2031529130 @default.
• W2017180975 cites W2060742905 @default.
• W2017180975 cites W2094381047 @default.
• W2017180975 cites W2101578637 @default.
• W2017180975 cites W2107632648 @default.
• W2017180975 cites W2108063263 @default.
• W2017180975 cites W2117923849 @default.
• W2017180975 cites W2139964006 @default.
• W2017180975 cites W2142630559 @default.
• W2017180975 cites W2152996957 @default.
• W2017180975 cites W2167507894 @default.
• W2017180975 cites W2168013455 @default.
• W2017180975 doi "https://doi.org/10.1016/j.artmed.2014.11.001" @default.
• W2017180975 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25547266" @default.
• W2017180975 hasPublicationYear "2015" @default.
• W2017180975 type Work @default.
• W2017180975 sameAs 2017180975 @default.
• W2017180975 citedByCount "3" @default.
• W2017180975 countsByYear W20171809752016 @default.
• W2017180975 countsByYear W20171809752019 @default.
• W2017180975 crossrefType "journal-article" @default.
• W2017180975 hasAuthorship W2017180975A5075523751 @default.
• W2017180975 hasConcept C102230213 @default.
• W2017180975 hasConcept C104317684 @default.
• W2017180975 hasConcept C111599444 @default.
• W2017180975 hasConcept C111829913 @default.
• W2017180975 hasConcept C135983454 @default.
• W2017180975 hasConcept C1491633281 @default.
• W2017180975 hasConcept C150194340 @default.
• W2017180975 hasConcept C161733203 @default.
• W2017180975 hasConcept C40767141 @default.
• W2017180975 hasConcept C54355233 @default.
• W2017180975 hasConcept C70721500 @default.
• W2017180975 hasConcept C86803240 @default.
• W2017180975 hasConcept C92087593 @default.
• W2017180975 hasConcept C95444343 @default.
• W2017180975 hasConceptScore W2017180975C102230213 @default.
• W2017180975 hasConceptScore W2017180975C104317684 @default.
• W2017180975 hasConceptScore W2017180975C111599444 @default.
• W2017180975 hasConceptScore W2017180975C111829913 @default.
• W2017180975 hasConceptScore W2017180975C135983454 @default.
• W2017180975 hasConceptScore W2017180975C1491633281 @default.
• W2017180975 hasConceptScore W2017180975C150194340 @default.
• W2017180975 hasConceptScore W2017180975C161733203 @default.
• W2017180975 hasConceptScore W2017180975C40767141 @default.
• W2017180975 hasConceptScore W2017180975C54355233 @default.
• W2017180975 hasConceptScore W2017180975C70721500 @default.
• W2017180975 hasConceptScore W2017180975C86803240 @default.
• W2017180975 hasConceptScore W2017180975C92087593 @default.
• W2017180975 hasConceptScore W2017180975C95444343 @default.
• W2017180975 hasLocation W20171809751 @default.
• W2017180975 hasLocation W20171809752 @default.
• W2017180975 hasOpenAccess W2017180975 @default.
• W2017180975 hasPrimaryLocation W20171809751 @default.
• W2017180975 hasRelatedWork W1981933257 @default.
• W2017180975 hasRelatedWork W1990425673 @default.
• W2017180975 hasRelatedWork W2002449019 @default.
• W2017180975 hasRelatedWork W2017101043 @default.
• W2017180975 hasRelatedWork W2031863945 @default.
• W2017180975 hasRelatedWork W2079316258 @default.
• W2017180975 hasRelatedWork W2083154457 @default.
• W2017180975 hasRelatedWork W2095425397 @default.
• W2017180975 hasRelatedWork W2113402490 @default.
• W2017180975 hasRelatedWork W2427350414 @default.
• W2017180975 isParatext "false" @default.
• W2017180975 isRetracted "false" @default.
• W2017180975 magId "2017180975" @default.
• W2017180975 workType "article" @default.