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SUMMARY:Big Molecules and Small Particles - Professor Lennart Lindfors\, U
 niversity of Gothenburg
DTSTART:20180117T141500Z
DTEND:20180117T151500Z
UID:TALK86961@talks.cam.ac.uk
CONTACT:Lisa Masters
DESCRIPTION:Modified messenger RNA constitues a new intresting approach fo
 r transient protein expression in different therapies. Based on learnings 
 from DNA delivery the intracellular delivery of such macromolecules remain
 s a challenge. In our work we have prepared so called lipid nanoparticles 
 (LNPs)\, containing several copies of mRNA in each\, using microfluidic mi
 xing. The size of such LNPs can be easily manipulated using different amou
 nts of PEG-ylated stabilizers resulting in rather monodisperse nanoparticl
 es having number-averaged diameters between 50 and 150 nm. In these studie
 s we have been using a erythropoietin mRNA (5-methylcytidine\, pseudouridi
 ne). The focus of this presentation will be on structural studies using cr
 yo-transmission electron microscopy\, small-angle x-ray and neutron scatte
 ring for LNPs of different sizes.  For the case of neutron scattering usin
 g contrast variation is especially informative. We use this information to
  enable more detailed studies of the LNP internal structure and to tailor 
 the LNP surface composition. Furthermore\, we have also performed in vitro
  cell (human hepatocytes and adipocytes) and in vivo (intravenous and subc
 utaneous administration) studies studies measuring both LNP uptake and the
  concurrent protein expression with the ambition to correlate LNP stucture
  to their biological function.
LOCATION:Department of Chemistry\, Cambridge\, Unilever lecture theatre
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