Correlation Engine 2.0
Clear Search sequence regions

  • amine (1)
  • cytosol (2)
  • ester (1)
  • factors (1)
  • gene (1)
  • gene transfer techniques (1)
  • humans (1)
  • molecular probe (3)
  • nucleic acids (1)
  • renilla (3)
  • rna (2)
  • spleens (1)
  • Sizes of these terms reflect their relevance to your search.

    Endosomal escape is a key step for intracellular drug delivery of nucleic acids, but reliable and sensitive methods for its quantitation remain an unmet need. In order to rationally optimize the mRNA transfection efficiency of a library of polymeric materials, we designed a deactivated Renilla luciferase-derived molecular probe whose activity can be restored only in the cytosol. This probe can be coencapsulated with mRNA in the same delivery vehicle, thereby accurately measuring its endosomal escape efficiency. We examined a library of poly(amine-co-ester) (PACE) polymers with different end groups using this probe and observed a strong correlation between endosomal escape and transfection efficiency (R2 = 0.9334). In addition, we found that mRNA encapsulation efficiency and endosomal escape, but not uptake, were determinant factors for transfection efficiency. The polymers with high endosomal escape/transfection efficiency in vitro also showed good transfection efficiency in vivo, and mRNA expression was primarily observed in spleens after intravenous delivery. Together, our study suggests that the luciferase probe can be used as an effective tool to quantitate endosomal escape, which is essential for rational optimization of intracellular drug delivery systems.


    Yuhang Jiang, Qiao Lu, Yongheng Wang, Emily Xu, Alison Ho, Priya Singh, Yifei Wang, Zhaozhong Jiang, Fan Yang, Gregory T Tietjen, Peter Cresswell, W Mark Saltzman. Quantitating Endosomal Escape of a Library of Polymers for mRNA Delivery. Nano letters. 2020 Feb 12;20(2):1117-1123

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 32003222

    View Full Text