Monitoring Translation Activity of mRNA-Loaded Nanoparticles in Mice

Molecular Pharmaceutics
Sebastian RosigkeitErnesto Bockamp

Abstract

Targeting mRNA to eukaryotic cells is an emerging technology for basic research and provides broad applications in cancer immunotherapy, vaccine development, protein replacement, and in vivo genome editing. Although a plethora of nanoparticles for efficient mRNA delivery exists, in vivo mRNA targeting to specific organs, tissue compartments, and cells remains a major challenge. For this reason, methods for reporting the in vivo targeting specificity of different mRNA nanoparticle formats will be crucial. Here, we describe a straightforward method for monitoring the in vivo targeting efficiency of mRNA-loaded nanoparticles in mice. To achieve accurate mRNA delivery readouts, we loaded lipoplex nanoparticles with Cre-recombinase-encoding mRNA and injected these into commonly used Cre reporter mouse strains. Our results show that this approach provides readouts that accurately report the targeting efficacy of mRNA into organs, tissue structures, and single cells as a function of the used mRNA delivery system. The method described here establishes a versatile basis for determining in vivo mRNA targeting profiles and can be systematically applied for testing and improving mRNA packaging formats.

References

Apr 12, 2001·BMC Developmental Biology·S SrinivasF Costantini
Oct 26, 2006·Applied Microbiology and Biotechnology·Sonja Berensmeier
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Limor LandsmanSteffen Jung
Sep 18, 2007·Genesis : the Journal of Genetics and Development·Mandar Deepak MuzumdarLiqun Luo
Nov 12, 2009·Methods in Enzymology·T K RitchieS G Sligar
Jan 11, 2011·Nature Biotechnology·Michael S D KormannCarsten Rudolph
Jan 13, 2012·Cancer Research·John C CastleUgur Sahin
Jan 17, 2012·Nature Methods·Timothy RaganPavel Osten
Jan 9, 2013·Methods in Molecular Biology·Ewa Grudzien-NogalskaRobert E Rhoads
Apr 30, 2013·Development, Growth & Differentiation·Takaya Abe, Toshihiko Fujimori
Sep 23, 2014·Nature Reviews. Drug Discovery·Ugur SahinÖzlem Türeci
Apr 23, 2015·Nature·Sebastian KreiterUgur Sahin
Jan 2, 2016·Science·Mohammadsharif TabebordbarAmy J Wagers
Jul 7, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jasdave S ChahalDaniel G Anderson
Sep 20, 2016·Genome Génome / Conseil National De Recherches Canada·Junshuang JiaWeiwang Gu
Feb 17, 2017·Proceedings of the National Academy of Sciences of the United States of America·Suvasini RamaswamyInder M Verma
May 2, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kapil BahlGiuseppe Ciaramella
Jun 13, 2017·Nature Medicine·Christiane R StadlerUgur Sahin
Jun 29, 2017·Genome Medicine·James C KaczmarekDaniel G Anderson
Jul 5, 2017·Chemical & Pharmaceutical Bulletin·Shintaro Fumoto, Koyo Nishida
Dec 13, 2017·Molecular Pharmaceutics·Antje ZillerPeter Langguth

❮ Previous
Next ❯

Citations

Sep 13, 2020·International Journal of Molecular Sciences·Shuqin XuLu Zhang
Feb 24, 2020·Biotechnology Advances·Yuhua WengYuanyu Huang
Jul 6, 2020·Advanced Drug Delivery Reviews·Dominik WitzigmannRoy van der Meel
Oct 28, 2020·Langmuir : the ACS Journal of Surfaces and Colloids·Lukas UebbingPeter Langguth
Jul 3, 2021·Pharmaceutics·Maarten K Nijen TwilhaarJoke M M den Haan
Aug 1, 2021·International Journal of Cancer. Journal International Du Cancer·Sebastian RosigkeitErnesto Bockamp

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.