Zooming in on the target: transductional and transcriptional targeting.

Research output: Contribution to journalEditorial

Abstract

The therapeutic index of gene delivery vectors can be significantly improved by targeting gene delivery at the level of transduction,transcription or genomic integration. Transductional
targeting can be achieved by modifying the vector capsid or envelope in order to deliver the therapeutic gene into the appropriate target cells. We have previously demonstrated that AAV9
vectors have an exquisite cardiac tropism that can be exploited to develop improved gene therapy approaches for cardiovascular disease. Moreover, this cardiotropism of AAV9 offers unprecedented
opportunities to assess the function of genes or miRNAs in the heart without having to resort to the generation of transgenic mouse models. We have established proof-of-concept that AAV9-mediated delivery of TSP-2 protects against age-related or inflammatory cardiomyopathy. Transductional targeting to the
liver could be achieved using either AAV8 or AAV9 serotypes yielding supra-physiologic clotting factor IX expression levels.
To achieve transcriptional targeting we validated a novel datamining algorithm, that allowed us to identify specific combinations of evolutionary conserved cardiac-specific or liver-specific
transcription factor binding sites (TFBS). These TFBS combinations represent common denominators among highly expressed cardiac-specific or liver-specific genes, respectively. Consequently,
robust cardiac or liver-specific gene expression could be achieved using AAV vectors containing these de novo designed tissue-specific expression cassettes.
Original languageEnglish
Pages (from-to)13-13
Number of pages1
JournalHum Gene Ther
Volume22
Issue numberOctober
Publication statusPublished - 2011

Keywords

  • AAV9

Fingerprint

Dive into the research topics of 'Zooming in on the target: transductional and transcriptional targeting.'. Together they form a unique fingerprint.

Cite this