Compact polyethylenimine-complexed mRNA vaccines

Moreno Herrero J, Stahl T, Erbar S, Maxeiner K, Schlegel A, Bacic T, Schumacher J, Cavalcanti L, Schroer M, Svergun D, Sahin U, Haas H, Nature Nanotechnology (2025) DOI

SASDRL9 – single self-amplifying RNA + 50 mM NaCl

self-amplifying RNA
MWI(0) 3300 kDa
MWexpected 3030 kDa
VPorod 112000 nm3
log I(s) 1.28×107 1.28×106 1.28×105 1.28×104
self-amplifying RNA small angle scattering data  s, nm-1
ln I(s)
self-amplifying RNA Guinier plot ln 1.29×107 Rg: 30.7 nm 0 (30.7 nm)-2 s2
(sRg)2I(s)/I(0)
self-amplifying RNA Kratky plot 1.104 0 √3 sRg
p(r)
self-amplifying RNA pair distance distribution function Rg: 32.7 nm 0 Dmax: 107.4 nm

Data validation

Fits and models

log I(s)
 s, nm-1
self-amplifying RNA DAMMIF model
Synchrotron SAXS data from solutions of single self-amplifying RNA in 5% w/v D-Glucose, 10mM MES (2-(N-morpholino)ethanesulfonic acid), 50 mM NaCl in double distillated sterile/RNAse free water, pH 6.1 were collected on the EMBL P12 beam line at PETRA III (DESY, Hamburg, Germany) using a Pilatus 6M detector at a sample-detector distance of 3 m and at a wavelength of λ = 0.123985 nm (I(s) vs s, where s = 4πsinθ/λ, and 2θ is the scattering angle). One solute concentration of 0.20 mg/ml was measured at 23°C. 20 successive 0.100 second frames were collected. The data were normalized to the intensity of the transmitted beam and radially averaged; the scattering of the solvent-blank was subtracted.

Self-amplifying RNA (saRNA) in presence of 50 mM NaCl resulting in a mild level of compaction. DAM volume: 26.9 * 10³ nm³. MW: 3.3 MDa (monomer).

self-amplifying RNA (saRNA)
Mol. type   RNA
Olig. state   Monomer
Mon. MW   3030 kDa
Sequence   FASTA