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I've read that the Pfizer mRNA vaccine is delivered to the cell by encapsulating the fragile mRNA into a lipid nanoparticle. However, the lipid has to be PEGylated in order to avoid immunogenecity. Why is that? How does PEGylation reduce immunogenicity in general?

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Lipid nano particles are bound by serum proteins, the opsonins which are part of the innate system and are subsequently eliminated from the body by uptake through macrophages.

Binding PEG to the surface of these particles increases their hydrophilicity (and obviously creates a hydrate hull around the particles) and functions as well as a steric barrier. Both measures prevent the opsonins from binding the particles and thus marking them for removal, which extends their half-life (see the references for more details).

References:

  1. PEGylated liposomes: immunological responses
  2. Rationale and Application of PEGylated Lipid-Based System for Advanced Target Delivery of siRNA
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