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In: Biology

Briefly speculate how complexation with certain PEGylated polycationic polymers such as PLL-PEG can increase the potency...

Briefly speculate how complexation with certain PEGylated polycationic polymers such as PLL-PEG can increase the potency of hydrophobically modified RNAi molecules.

Solutions

Expert Solution

The presence of positive charges on the surface of PLL/siRNA complexes is believed to enhance cell internalization. However, interaction of the positively charged PLL/siRNA complexes with negatively charged serum proteins may cause undesired aggregation and RES uptake, which consequently decrease the therapeutic outcome of siRNA.

Modification of PLL with polysaccharides, PEG, or other water-soluble polymers is the major strategy to enhance the systemic circulation profile of PLL/siRNA complexes by decreasing nonspecific interaction with blood components.

PEGylation of PLL leads to formation of particles with a core-shell structure. Such particles contain a cationic fragment in the inner core that helps to condense nucleic acids. The uncharged hydrophilic PEG outer layer helps to reduce particle size, cytotoxicity, and nonspecific interaction with blood components, leading to prolonged systemic circulation.


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