Application of enhanced biophysical strategies to determine ASO/target RNA binding affinity and kinetics

Michael Lerche

Submitted to SASBDB: 2022 Mar 8 Published in SASBDB: 2025 Mar 8

SASDNX6 – ASO1 DNA in the absence of target RNA Sample: LNA-DNA-LNA monomer, 4 kDa DNA Buffer: phosphate buffered saline, pH: 7.4 Experiment: SAXS data collected at B21, Diamond Light Source on 2021 Oct 21 RgGuinier 1.3 nm Dmax 4.0 nm VolumePorod 4 nm3

SASDNY6 – ASO2 DNA in the absence of target RNA Sample: MOE PS gapmers 3-8-3 monomer, 4 kDa DNA Buffer: phosphate buffered saline, pH: 7.4 Experiment: SAXS data collected at B21, Diamond Light Source on 2021 Oct 21 RgGuinier 1.4 nm Dmax 4.3 nm VolumePorod 5 nm3

SASDNZ6 – ASO3 RNA in the absence of target RNA Sample: OME ASO monomer, 4 kDa RNA Buffer: phosphate buffered saline, pH: 7.4 Experiment: SAXS data collected at B21, Diamond Light Source on 2021 Oct 21 RgGuinier 1.4 nm Dmax 4.0 nm VolumePorod 7 nm3

SASDN27 – ASO1 DNA in the presence target RNA Sample: LNA-DNA-LNA monomer, 4 kDa DNA PSCK9, 24mer ASO binding site monomer, 8 kDa RNA Buffer: phosphate buffered saline, pH: 7.4 Experiment: SAXS data collected at B21, Diamond Light Source on 2021 Oct 21 RgGuinier 1.9 nm Dmax 6.2 nm VolumePorod 15 nm3

SASDN37 – ASO2 DNA in the presence of target RNA Sample: MOE PS gapmers 3-8-3 monomer, 4 kDa DNA PSCK9, 24mer ASO binding site monomer, 8 kDa RNA Buffer: phosphate buffered saline, pH: 7.4 Experiment: SAXS data collected at B21, Diamond Light Source on 2021 Oct 21 RgGuinier 2.1 nm Dmax 6.4 nm VolumePorod 16 nm3

SASDN47 – ASO3 RNA in the presence of target RNA Sample: OME ASO monomer, 4 kDa RNA PSCK9, 24mer ASO binding site monomer, 8 kDa RNA Buffer: phosphate buffered saline, pH: 7.4 Experiment: SAXS data collected at B21, Diamond Light Source on 2021 Oct 21 RgGuinier 1.9 nm Dmax 6.2 nm VolumePorod 16 nm3