Morpholino-mediated increase in soluble Flt-1 expression results in decreased ocular and tumor neovascularization.

ABSTRACT:

Background

Angiogenesis is a key process in several ocular disorders and cancers. Soluble Flt-1 is an alternatively spliced form of the Flt-1 gene that retains the ligand-binding domain, but lacks the membrane-spanning and intracellular kinase domains of the full-length membrane bound Flt-1 (mbFlt-1) protein. Thus, sFlt-1 is an endogenous inhibitor of VEGF-A mediated angiogenesis. Synthetic mopholino oligomers directed against splice site targets can modulate splice variant expression. We hypothesize that morpholino-induced upregulation of sFlt-1 will suppress angiogenesis in clinically relevant models of macular degeneration and breast cancer.

Methods and findings

In vivo morpholino constructs were designed to target murine exon/intron 13 junction of the Flt-1 transcript de

SUBMITTER: Owen LA 

PROVIDER: S-EPMC3305322 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature