ADIPOCYTE-SPECIFIC CONSTRUCTS AND METHODS FOR INHIBITING PLATELET-TYPE 12 LIPOXYGENASE EXPRESSION

摘要

The present invention is directed to constructs, compositions and methods for modulating platelet-type 12 lipoxygenase (12-LO) in adipose tissue in vivo. Specifically, the invention provides constructs encoding expression-inhibiting oligonucleic acids, e.g. antisense and RNA interfering (RNAi) molecules, targeted to a platelet-type 12-LO gene or a transcript thereof, which are capable of reducing or silencing platelet-type 12-LO expression specifically in adipocytes and pre-adipocytes. Vectors comprising these constructs (including, but not limited to, viral vectors), compositions comprising them and methods of using same for the treatment and amelioration of conditions associated with excess fat cell mass and obesity are also provided.

主权项

1. A recombinant nucleic acid construct suitable for the treatment of humans comprising at least one adipose-specific transcription regulating sequence operably linked to at least one nucleic acid sequence, wherein the at least one nucleic acid sequence encodes an oligonucleic acid comprising at least one sequence complementary to a platelet-type lipoxygenase (platelet-type 12-LO) gene or transcript thereof, and wherein the oligonucleic acid specifically inhibits or reduces the expression of platelet-type 12-LO, containing at least one adipose-specific transcription regulating sequence containing a C/EBP binding site, an SpI binding site or combinations thereof.