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RNA Biol. 2011 Jan-Feb;8(1):35-43. Epub 2011 Jan 1.

Determinants of intracellular RNA pharmacokinetics: Implications for RNA-based immunotherapeutics.

Author information

1
Center for Translational Oncology and Immunology (TrOn), Mainz, Germany.

Abstract

RNAs with optimized properties are increasingly investigated as a tool to deliver the genetic information of complete antigens into professional antigen-presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. As the dose of the antigen and duration of its presentation are critical factors for generating strong and sustained antigen-specific immune responses, improvement of the immunobioavailability of RNA-based vaccines has been a recurrent subject of research. Substantial increase of the amount of antigen produced from RNA can be achieved by optimizing RNA stability and translational efficiency. Both features are determined by cis-acting elements in the RNA, namely the 5' cap, the poly(A) tail, and the sequence of the coding and non-coding regions, which interact with corresponding trans-acting factors. This article summarizes recent developments in identifying optimized RNA for expression of foreign proteins in dendritic cells, as well as their implications for immunotherapy based on antigen-encoding RNA.

PMID:
21289486
[Indexed for MEDLINE]

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