Search

Efficient and targeted delivery of nucleic acids is critical for realizing the full therapeutic potential of gene editing, vaccines and RNA-based drugs, and emerging delivery platforms offer innovative solutions through their diverse architectures, tunable properties and distinct biological interactions. In this Viewpoint, researchers working across different delivery platforms — including lipid nanoparticles, synthetic polymers, peptide amphiphiles, coacervate microdroplets, DNA nanostructures and extracellular vesicles — discuss the most promising directions and the main challenges in shaping the future of nucleic acid delivery.

The engineering of biomimetic materials is accelerated by combining high-throughput RNA sequencing and proteomics.

Sucker ring teeth from squid and cuttlefish represent rare examples of thermoplastic biopolymers. Here, the authors demonstrate how these materials may be processed for implementation in biomedical and 3D printing applications.

The squid beak displays a 200-fold stiffness gradient across its length. A battery of experiments, including ‘omics analysis and rheological measurements, now identifies two protein families that infiltrate and cross-link a porous chitin network to generate variable stiffness.

Phase-separating peptide (PSP) coacervate microdroplets (CMs) have emerged as promising intracellular delivery vectors, but the molecular grammar governing intracellular uptake and release kinetics of CMs is elusive. Here, the authors systematically manipulate the sequence of PSPs to establish molecular guidelines for designing and optimizing PSP CM-based intracellular delivery systems.

Ticks secrete a protein-based saliva that hardens into a cement, ensuring that they firmly attach to their host. Now, insight is provided into the phase transitions and adhesive properties of a disordered glycine-rich protein found in such secretions.

Interfacial water constitutes a formidable barrier to strong surface bonding, hampering the development of water-resistant synthetic adhesives. Here, the authors elucidate the precise time-regulated secretion of mussel adhesive proteins in Perna viridis, probing their surface structures and subsequent roles.

Coacervate microdroplets formed from pH- and redox-responsive peptides and self-assembled by liquid–liquid phase separation have been shown to quickly recruit macromolecular therapeutics—such as peptides, large proteins and mRNAs—and directly enter the cytosol of cells via a non-endocytic pathway. The subsequent release of therapeutic cargo is mediated by endogenic glutathione.

Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins plays an important part in the formation of extracellular biological materials. Here, the authors show that repeats of the peptide motif GHGLY are necessary for the LLPS of pH-responsive histidine-rich squid beak proteins.

Bioelastomers generally show elasticity similar to that of rubber, which originates from entropic forces linked to deformation. It is now shown that in the egg capsule of a large marine shell, the elasticity is instead based on a structural transition. The results could have a significant impact on engineering protective encapsulating systems inspired by natural elastomers.

Nanoindentation and spectroscopy measurements show that the impact surface of the dactyl club—a hammer-like device that stomatopods use to shatter hard seashells—has a quasi-plastic response that enhances the damage tolerance of the clubs.

The raptorial appendages of stomatopods are known to inflict large impact forces at high speeds, while exhibiting large damage tolerance. Here, the authors study the structure, distribution and nanomechanical properties of mineral phases in stomatopod's clubs, finding that calcium sulphate is co-localized with crystalline fluorapatite.

Biobased materials are of interest for many applications. Here the authors report insect-derived peptides that self-assemble into hollow nanocapsules through a gradient-driven, single-step, solvent exchange process, enabling the encapsulation of diverse cargoes with potential for drug delivery applications.

Peptides are small yet versatile building blocks of biomaterials. This Comment highlights recent progress in the design of liquid-like microdroplets, or coacervates, based on peptides and produced through liquid–liquid phase separation. This emerging platform holds promise as efficacious delivery vehicles for multi-purpose biomedical applications.

Fluid protein condensates are utilized as precursors in the production of high-performance biological fibres, adhesives and composites. This Review outlines the key role of condensates in the formation of several well-studied biological materials and highlights bioengineered materials with biomedical applications that draw inspiration from these archetypes.

Metallic surfaces are often coated with corrosion inhibitors to prevent damage but these are typically toxic to the environment. Here, a recombinant adhesive cement protein from barnacles is shown to effectively protect steel against corrosion under marine environment conditions.

Peptide-based coacervates display interesting properties for biomedical applications, however, the link between peptide structure and coacervate material properties remains unclear. Here, the authors report a direct correlation between the primary and secondary structures of the peptides and the viscoelastic properties of the coacervates.