This allows elucidating the individual contribution of the Gaiisoforms to the ischemic reperfusion injury in the heart. Furthermore with this approach an up regulation of the remaining isoform may be prevented. Whereas an appropriate Gai2-model is available the corresponding Gai3-mouse model has not been created so far. In conclusion, we provide strong evidence that both the deficiency for Gai2 and for Gai3 has profound and opposite effects on IR injury in mice. This may open the rationale to develop biased GiPCR drugs which may allow a different regulation of Gai2 and Gai3 by the same receptor. Targeting transcription factors therapeutically remains a challenge, as they are not conventional ����druggable���� molecules, such as proteins with enzymatic activity that can be inhibited by small molecules or receptor proteins that can be targeted by antibodies. The discovery of RNA interference has revolutionized this field as, theoretically, any target can be hit with this strategy. RNA interference consists of a doublestranded small interfering RNA with a length of about 20�C30 nucleotides that leads to a sequence specific enzymatic cleavage of a target mRNA through complementary base pairing. Although promising, the TRAM 39 clinical TFM-4AS-1 application of siRNAs continues to face problems related to their effective cellular delivery. Therefore, the development of delivery systems that can protect and transport siRNA is a field of active research. Chitosan is a polymer of b-1-4 N-acetylglucosamine and D-glucosamine residues derived by partial deacetylation of chitin. Since this is a natural, biocompatible, biodegradable, mucoadhesive and non-toxic polymer with a relative low-cost production, it has been broadly studied for the delivery of both plasmid DNA and siRNA due to its capacity, when positively charged, to protect nucleic acids from degradation by endonucleases. Primary amine residues of CH are protonated at pH values below its pKa giving it the capacity to complex anionic compounds, such as the phosphate groups of nucleic acids, enabling the formation of nanoparticles by electrostatic interactions between both functional groups. A number of CH modifications have been proposed to enhance the efficacy of CH as a nucleic acid vector, namely the introduction of imidazole moieties into the CH backbone which has proven effective in promoting the escape of the nanoparticles from the endocytic pathway. The partial quaternization of CH gives origin to trimethylchitosan, which has fixed positive charges, being soluble at a wider pH range and exhibiting enhanced mucoadhesive potential. CDX2, a transcription factor belonging to the caudal-related homeobox gene family, is a master regulator of intestinal cell survival and differentiation.