Minimizing the off-target frequency of the CRISPR/Cas9 system zwitterionic polymer conjugation and peptide fusion.

The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated protein 9 (Cas9) system is a powerful genome-editing tool that is widely used in many different applications. However, the high-frequency mutations induced by RNA-guided Cas9 at sites other than the intended on-target sites are a major concern that impedes therapeutic and clinical applications. A deeper analysis shows that most off-target events result from the non-specific mismatch between single guide RNA (sgRNA) and target DNA.

Zwitterlation mitigates protein bioactivity loss over PEGylation.

Conjugation with poly(ethylene glycol) (PEG) or PEGylation is a widely used tool to overcome the shortcomings of native proteins, such as poor stability, inadequate pharmacokinetic (PK) profiles, and immunogenicity. However, PEGylation is often accompanied by an unwanted detrimental effect on bioactivity, particularly, resulting from the amphiphilic nature of PEG. This is especially true for PEGylated proteins with large binding targets.

Controlled heterogeneous stem cell differentiation on a shape memory hydrogel surface.

The success of stem cell therapies is highly dependent on the ability to control their programmed differentiation. So far, it is commonly believed that the differentiation behavior of stem cells is supposed to be identical when they are cultured on the same homogeneous platform. However, in this report, we show that this is not always true.

Redox-triggered self-rolling robust hydrogel tubes for cell encapsulation.

In this study, mechanically strong hydrogels are synthesized by photopolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine, poly(ethylene glycol) methacrylate, and disulfide-containing cross-linker, N'N-bis(acryloyl)cystamine. The bilayer hydrogel with distinct cross-linking density is shown to self-roll into a 3D tube, which could still be well reinforced by hydrogen bondings, upon exposing reductants such as 1,4-dithio-DL-threitol (DTT) or L-glutathione (GSH), because the redox-induced cleavage of disulfide bonds results in the imbalanced internal shrinking stress between two layers. At an intracellular level of GSH, model L929 cells-seeded bilayer gel sheet could curl up into a 3D tubular scaffold where the cells maintained good viability.

Double hydrogen-bonding pH-sensitive hydrogels retaining high-strengths over a wide pH range.

Traditional pH-sensitive hydrogels inevitably suffer strength deterioration while the responsive weak acid or base groups are in the ionized state. In this study, we report on a facile approach to fabricate a novel pH-sensitive high-strength hydrogel from copolymerization of two hydrogen-bonding motif-containing monomers, 3-acrylamidophenylboronic acid and 2-vinyl-4,6-diamino-1,3,5-triazine with a crosslinker N,N-methylenebisacrylamide through hydrophilic optimization of the comonomer oligo(ethylene glycol) methacrylate. The double hydrogen bonding hydrogel exhibits both high tensile and compressive strengths over a broad pH range due to the unique ability to maintain at least one type of hydrogen-bonding crosslink over the whole course of pH change.

High-strength hydrogel as a reusable adsorbent of copper ions.

A mechanically strong hydrogel was prepared by photoinitiated polymerization of oligo(ethylene glycol) methacrylate (OEGMA), 2-vinyl-4,6-diamino-1,3,5-triazine (VDT) and cross-linker N,N'-methylenebisacrylamide (MBAA). Introduction of the monomer VDT considerably strengthened the mechanical properties of the hydrogel by self-hydrogen bonding of diaminotriazine, and enhanced the adsorption of copper ion onto the hydrogel by chelation between amino groups and metal ion. Adsorption studies were carried out by varying the OEGMA/VDT ratio, contact time, pH value, counterion and initial concentration of Cu(2+) ions.

Zinc ion uniquely induced triple shape memory effect of dipole-dipole reinforced ultra-high strength hydrogels.

In this study, we demonstrate that dipole-dipole interaction can be employed to not only tremendously enhance the mechanical properties of hydrogel, but also impart the gel to an amazing ability to memorize two temporary shapes. Cross-linked hydrogels synthesized by copolymerization of acrylonitrile, a dipole-dipole containing monomer and hydrophilic comonomer are shown to exhibit triple shape memory (SM) triggered by the dynamic association and dissociation of dipole-dipole pairing between cynao groups uniquely responding to zinc ion species and concentration. This approach contributes to design and fabrication of novel SM hydrogels in a distinct way from conventional SM materials.