Cowpea Chlorotic Mottle Virus‐Like Particles as Potential Platform for Antisense Oligonucleotide Delivery in Posterior Segment Ocular Diseases

Abstract

Due to its small size, easy accessibility and immune privileged environment, the eye represents an ideal target for therapeutic nucleic acids in the treatment of posterior segment ocular diseases, such as age‐related macular degeneration (AMD). Among nanocarriers that can be used to achieve nucleic acid delivery, virus‐like particles (VLPs) obtained from the Cowpea chlorotic mottle virus (CCMV) are an appealing platform, because of their loading capacity, ease of manufacture and amenability for functionalization. Herein, antisense oligonucleotide‐loaded CCMV nanoparticles, intended for intravitreal injection, are evaluated for selective silencing of miR‐23, an important target in AMD. CCMV nanoparticles loaded with anti‐miR‐23 locked nucleic acid and stabilized using the 3,3′‐dithiobis(sulfosuccinimidyl propionate) (DTSSP) cross‐linker, are assembled in vitro with a loading efficiency up to 80%. VLPs are found to be stable at 37 °C in the vitreous humor up to 24 hours. Nanoparticle cytotoxicity, cellular uptake and transfection efficacy are evaluated in endothelial cells. Selective miRNA down‐regulation is achieved by the loaded CCMV VLPs both in absence and presence of Lipofectamine, with efficacies of ≈40% and more than 80%, respectively. The authors' findings pave the way for the future development of CCMV nanoparticles as oligonucleotide delivery platform to treat posterior segment ocular diseases.

Efficient Purification of Cowpea Chlorotic Mottle Virus by a Novel Peptide Aptamer

“…Plant viruses and their respective virus-like particles (VLP) offer an exciting nanotechnological platform for a variety of applications. Their propensity to self-assemble into monodisperse and highly symmetric nanometer-range particles makes them obvious candidates for the entrapment and delivery of biomedically active cargos in vivo [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. In addition, the rigid protein capsids may be genetically or chemically modified to introduce (bio)chemical moieties to be displayed on the viruses’ surface [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

Efficient Purification of Cowpea Chlorotic Mottle Virus by a Novel Peptide Aptamer

“…MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content. monodisperse and highly symmetric nanometer-range particles makes them obvious candidates for the entrapment and delivery of biomedically active cargos in vivo [1][2][3][4][5][6][7][8][9][10]. In addition, the rigid protein capsids may be genetically or chemically modified to introduce (bio)chemical moieties to be displayed on the viruses' surface [11][12][13][14][15][16].…”

Engineered Plant Virus Complexes with a RANK Motif Modulator and Bone Targeting for Osteoporosis Treatment

“…41 Moreover, CCMV is regarded as a promising carrier because CCMV can not only encapsulate cargos, like RNAs, into its protein cage but also offer a powerful site for decoration with functional molecules on the surface. 42,43 In this study, the peptide was synthesized consisting of bone-targeting peptide Asp8 44 (BT) and the peptide derived from RANK Motif2/3 (RM), denoted as BTRM (SRPVQEQGGADDDDDDDD). Then, via chemical modification, BTRM was decorated onto the external surface of VNPs from CCMV (BTRM−VNPs).…”

“…Notably, interaction studies have proven the safety and non-infection of plant viruses and virus-like particles in mammals . Moreover, CCMV is regarded as a promising carrier because CCMV can not only encapsulate cargos, like RNAs, into its protein cage but also offer a powerful site for decoration with functional molecules on the surface. , …”