α-Tocopherol is a kind of vitamin E that is preferentially absorbed and accumulated in the body. It's a chiral molecule and has three stereocenters, and each of its eight stereoisomers is different in the configuration of those stereocenters.
Vitamin E comes in eight different forms, including four tocopherols and four tocotrienols. Both have a chromane ring with a hydroxyl group, which provides a hydrogen atom to reduce free radicals, and a hydrophobic side chain that can penetrate the biofilm. Vitamin E is fat-soluble, which exists in a variety of tissues and is absorbed in a variety of ways. The most common form, α- Tocopherol, is involved in molecular, cellular, and biochemical processes that are closely associated with overall lipoprotein and lipid homeostasis.
Short interfering RNAs (siRNAs) have the potential for therapeutic application in a wide spectrum of disorders including cancer, infectious diseases, and inherited diseases. Scientists used α-tocopherol (vitamin E) as a carrier molecule of siRNA in vivo, and α- tocopherol has its physiological pathway to enter most organs. The α-tocopherol was covalently bound to the antisense strand of 27/29-mer siRNA at the 5'-end (Toc-siRNA). The 27/29-mer Toc-siRNA was designed to be cleaved by Dicer, producing a mature form of 21/21-mer siRNA after releasing α-tocopherol. The C6 hydroxyl group associated with antioxidant activity in α-tocopherol was eliminated. This vector has showed that Toc-siRNA can effectively reduce the expression of target mRNA in vivo. Biochemical and pathological analysis revealed no interferon (IFNs) or other significant side effects. These results suggest that Toc-siRNA can effectively and safely participate in siRNA-mediated gene silencing in vivo.
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