Preparation and Biological Properties of Oligonucleotide-Functionalized Virus-like Particles

被引:1
作者
Hincapie, Robert [1 ]
Bhattacharya, Sonia [1 ]
Keshavarz-Joud, Parisa [1 ]
Chapman, Asheley P. [1 ]
Crooke, Stephen N. [1 ]
Finn, M. G. [1 ,2 ]
机构
[1] Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA
[2] Georgia Inst Technol, Sch Biol Sci, Atlanta, GA 30332 USA
基金
美国国家卫生研究院;
关键词
AZIDE-ALKYNE CYCLOADDITION; SPHERICAL NUCLEIC-ACIDS; CELLULAR UPTAKE; DNA; NANOPARTICLE; DELIVERY; PERFORMANCE; CAPSIDS;
D O I
10.1021/acs.biomac.3c00178
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Oligonucleotides are powerful molecules for programmingfunctionand assembly. When arrayed on nanoparticle scaffolds in high density,the resulting molecules, spherical nucleic acids (SNAs), become imbuedwith unique properties. We used the copper-catalyzed azide-alkynecycloaddition to graft oligonucleotides on Q beta virus-like particlesto see if such structures also gain SNA-like behavior. Copper-bindingligands were shown to promote the click reaction without degradingoligonucleotide substrates. Reactions were first optimized with asmall-molecule fluorogenic reporter and were then applied to the morechallenging synthesis of polyvalent protein nanoparticle-oligonucleotideconjugates. The resulting particles exhibited the enhanced cellularuptake and protection from nuclease-mediated oligonucleotide cleavagecharacteristic of SNAs, had similar residence time in the liver relativeto unmodified particles, and were somewhat shielded from immune recognition,resulting in nearly 10-fold lower antibody titers relative to unmodifiedparticles. Oligonucleotide-functionalized virus-like particles thusprovide an interesting option for protein nanoparticle-mediated deliveryof functional molecules.
引用
收藏
页码:2766 / 2776
页数:11
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