Abstract: The small interfering RNA (siRNA) alters the
regulatory role of mRNA during gene expression by translational
inhibition. Recent studies show that upregulation of mRNA because
serious diseases like cancer. So designing effective siRNA with good
knockdown effects plays an important role in gene silencing. Various
siRNA design tools had been developed earlier. In this work, we are
trying to analyze the existing good scoring second generation siRNA
predicting tools and to optimize the efficiency of siRNA prediction
by designing a computational model using Artificial Neural Network
and whole stacking energy (%G), which may help in gene silencing
and drug design in cancer therapy. Our model is trained and tested
against a large data set of siRNA sequences. Validation of our results
is done by finding correlation coefficient of experimental versus
observed inhibition efficacy of siRNA. We achieved a correlation
coefficient of 0.727 in our previous computational model and we
could improve the correlation coefficient up to 0.753 when the
threshold of whole tacking energy is greater than or equal to -32.5
kcal/mol.
Abstract: Non-viral gene carriers composed of biodegradable
polymers or lipids have been considered as a safer alternative for gene
carriers over viral vectors. We have developed multi-functional
nano-micelles for both drug and gene delivery application.
Polyethyleneimine (PEI) was modified by grafting stearic acid (SA)
and formulated to polymeric micelles (PEI-SA) with positive surface
charge for gene and drug delivery. Our results showed that PEI-SA
micelles provided high siRNA binding efficiency. In addition, siRNA
delivered by PEI-SA carriers also demonstrated significantly high
cellular uptake even in the presence of serum proteins. The
post-transcriptional gene silencing efficiency was greatly improved by
the polyplex formulated by 10k PEI-SA/siRNA. The amphiphilic
structure of PEI-SA micelles provided advantages for multifunctional
tasks; where the hydrophilic shell modified with cationic charges can
electrostatically interact with DNA or siRNA, and the hydrophobic
core can serve as payloads for hydrophobic drugs, making it a
promising multifunctional vehicle for both genetic and chemotherapy
application.