2019
DOI: 10.1021/acs.bioconjchem.9b00731
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Versatile Reversible Cross-Linking Strategy to Stabilize CCMV Virus Like Particles for Efficient siRNA Delivery

Abstract: Virus like particles obtained from the Cowpea Chlorotic Mottle Virus (CCMV) represent an innovative platform for drug delivery applications. Their unique reversible self-assembly properties as well as their suitability for both cargo loading and functionalization make them a versatile scaffold for numerous purposes. One of the main drawbacks of this platform is however its limited stability at physiological conditions. Herein, we report the development of a general reversible cross-linking strategy involving t… Show more

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Cited by 27 publications
(28 citation statements)
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“…S5, ESI †). 30 This dual-step modication allowed us to limit both proposed mechanisms. A schematic overview of all samples used in this work and their relative stability (depending on the salt concentration) is reported in Table 1.…”
Section: Resultsmentioning
confidence: 99%
“…S5, ESI †). 30 This dual-step modication allowed us to limit both proposed mechanisms. A schematic overview of all samples used in this work and their relative stability (depending on the salt concentration) is reported in Table 1.…”
Section: Resultsmentioning
confidence: 99%
“…Previous efforts in this area have focused on developing a chemical methodology for strategic placement of disulfide functionalities in different drug delivery systems. [4][5][6][7][8][9] However, to our knowledge, engineering of disulfide functionality inside the interior of semi-synthetic protein assemblies have never been attempted. This is mainly attributed to the challenges associated with the system.…”
Section: Discussionmentioning
confidence: 99%
“…2 The highly reducing environment of cytoplasm of a living cell (1-10 mM glutathione (GSH)) compared to the extracellular medium (20-40 μM) is effectively used to design smart drug delivery systems. 3 To date, there are number of research groups working in this area to develop to disulfide containing amphiphilic polymers 4 , inorganic nanoparticles 5 , dendrimers 6 , virus-like particles 7 , peptide nucleic acids 8 and nucleic acid nanostructures 9 . However, the engineering of disulfide bond in these systems is relatively easy as they are completely synthetic, soluble in organic solvent and therefore amenable for structural modification.…”
Section: Introductionmentioning
confidence: 99%
“…Disassembly and reassembly are achieved through careful adjustment of the buffer conditions (see methods section). The negatively charged SDM RNAs interact with the CCMV CP, specifically with the highly positively-charged, arginine-rich binding domains at the N-terminus (amino acids 9-19; sequence: TRAQRRAAARK); 43,44 thus reconstitution of the chimeric CCMV VLP with the packaged SDM is achieved through electrostatic interactions rather than sequence-specific interactions, as was exploited for the Qβ Coomassie blue (protein stain). The VLPs have an overall negative charge and therefore migrate toward the anode.…”
Section: Production Of Vlp-based Sars-cov-2 Positive Controlsmentioning
confidence: 99%
“…For application in the clinic, it may be desired to stabilize the CCMV capsid through introduction of covalent bonds between CPs; this concept was recently demonstrated using a homobifunctional cross-linker 3, 3'-dithiobis (sulfosuccinimidylpropionate) (DTSSP) to form intra-particle cross-links between lysine side chains of adjacent CPs. 43 Next, and most importantly, we assayed for SDM stability. While no structural changes where observed for the Qβ 1P-C19 and Qβ 2P-C19 positive controls, RT-qPCR data indicate that the SDM copy number was reduced by 30-35% ( Table 2).…”
Section: Stability Of the Vlp-based Sars-cov-2 Positive Controlsmentioning
confidence: 99%