Tuning the Inter‐nanofibril Interaction To Regulate the Morphology and Function of Peptide/DNA Co‐assembled Viral Mimics

Abstract

The ability to tune the inter-subunit interaction within the virus capsid may be critical to assembly and biological function. This process was extended here with peptide/DNA co-assembled viral mimics. The resulting co-assemblies, formed and stabilized by both peptide nanofibril-DNA and peptide nanofibril-nanofibril interactions, were tuned through hydrophobic packing interactions of the peptide sequences. By strengthening peptide side-chain complementarity and/or elongating the peptide chain (from 4 to 8 residues), we report strengthening the inter-nanofibril interaction to create stable nanococoons that give high gene-transfection efficacy.

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

“…Chau and colleagues developed spherical virus-like nanococoons through coassembling pDNA and a short peptide K3C6SPD [ 80 ], which was consisted of an N -terminal cationic region for nucleic acid binding, a central β-sheet formation region for self-assembly and stabilization of the peptide/DNA nanococoons, and a C-terminal hydrophilic region for dispersion ( Figure 1 B). Further studies found that tuning the peptide sequence, such as changing side-chain hydrophobicity or β-sheet peptide length, significantly changes the stability of nanococoons, thus affecting their DNA transfection efficiency [ 84 ]. By incorporating four histidines at the N -terminus and two histidines within the central β-sheet region as pH-sensitive regions, as well as two aromatic benzylated cysteines CBzl within the central β-sheet region to promote self-assembly and inter-subunit association through π–π stacking and hydrophobic interactions, Chau et al further designed H4K5-HC Bzl C Bzl H peptide, which coassembled with pDNA into spherical VLPs [ 85 ].…”

Glycosylated Cell‐Penetrating Peptides (GCPPs)

“…The results reported herein highlight the potential of the glycosylationo fp enetratingp eptides to modulatetheir activity. [17][18][19][20][21][22][23][24][25] Interesting penetrating properties were further discovered in different naturala nd artificial structures, such as polyprolines, [26] guanidinyl glycosides, [27,28] b-peptides, [29] peptiden ucleic acids (PNAs), [30] nonpeptidic guanidinylated dendritic structures, [31] self-assembled nanofibers, [32,33] synthetic polymers, [34][35][36][37] supramolecular structures, [38][39][40] and polydisulfides. [14] These studies also showed that oligolysines were less effective than that of the oligoarginines analogues, [15] and triggered the development of synthetic penetrating oligoarginines.…”

“…[96][97][98] Glucose transporters (GLUTs) at the blood-brain barrier maintain the continuous high glucose and energyd emands of the brain, and thus, glucosec an be used to enhance the translocation of nanoparticles across the blood-brain barrier. [32] Recently,p enetrating polydisulfides have also been prepared with glycanm oieties to enhances olubility of the resulting polymer conjugates. [100] Furthermore, N-acetylgalactosamine (GalNAc) a-glycosylation to threonine or serine is included in the Tn antigen,w hichi so ne of the most specific human tumor associated carbohydrate antigens.…”

Rationally Designed Peptidyl Virus‐Like Particles Enable Targeted Delivery of Genetic Cargo

“…[2] Inspired by this,t here has been increasing enthusiasm to mimic viruses through the co-assembly of genetically engineered proteins and nucleic acids. [4] Forexample,Niand Chau reported the synergistic co-assembly of peptide and plasmid DNAi nto stable virus-like nanococoons with high gene-transfection efficacy. [4] Forexample,Niand Chau reported the synergistic co-assembly of peptide and plasmid DNAi nto stable virus-like nanococoons with high gene-transfection efficacy.…”

“…[3] Due to the structural simplicity,b iocompatibility,a nd versatility of peptides,i ncreasing studies are focusing on the construction of peptidyl virus-like particles (pVLPs) through the coassembly of peptides and nucleic acids. [4] Forexample,Niand Chau reported the synergistic co-assembly of peptide and plasmid DNAi nto stable virus-like nanococoons with high gene-transfection efficacy. [4a,5] Ryadnov et al designed at rifaceted coil-coil peptide helix, which self-assembles into monodispersed, anionic virus-like particles that adapt and transfer both RNAand DNA.…”