Spider silks are well known for their exceptional mechanical properties that are tougher than Kevlar and steel. However, the restricted production amounts from their native sources limit applications of spider silks. Over the decades, there have been significant interests in fabricating man-made silk fibers with comparable performance to natural silks, inspiring many efforts both for biosynthesizing recombinant spider silk proteins (spidroins) in amenable heterologous hosts and biomimetic spinning of artificial spider silks. These strategies provide promising routes to produce high-performance and functionally optimized fibers with diverse applications. Herein, we summarize the hosts that have been applied to produce recombinant spidroins. In addition, the fabrication and mechanical properties of recombinant spidroin fibers and their composite fibers are also introduced. Furthermore, we demonstrate the applications of recombinant spidroin-based fibers. Finally, facing the challenges in biosynthesis, scalable production, and hierarchical assembly of high-performance recombinant spidroins, we give a summary and perspective on future development.

Rheumatoid arthritis (RA) is a relatively common inflammatory disease that affects the synovial tissue, eventually results in joints destruction and even long-term disability. Although Janus kinase inhibitors (Jakinibs) show a rapid efficacy and are becoming the most successful agents in RA therapy, high dosing at frequent interval and severe toxicities cannot be avoided. Here, we developed a new type of fully compatible nanocarriers based on recombinant chimeric proteins with outstanding controlled release of upadacitinib. In addition, the fluorescent protein component of the nanocarriers enabled noninvasive fluorescence imaging of RA lesions, thus allowing real-time detection of RA therapy. Using rat models, the nanotherapeutic is shown to be superior to free upadacitinib, as indicated by extended circulation time and sustained bioefficacy. Strikingly, this nanosystem possesses an ultralong half-life of 45 h and a bioavailability of 4-times higher than pristine upadacitinib, thus extending the dosing interval from one day to 2 weeks. Side effects such as over-immunosuppression and leukocyte levels reduction were significantly mitigated. This smart strategy boosts efficacy, safety and visuality of Jakinibs in RA therapy, and potently enables customized designs of nanoplatforms for other therapeutics.

Functional proteins are the most versatile macromolecules. They can be obtained by extraction from natural sources or by genetic engineering technologies. The outstanding selectivity, specificity, binding activity, and biocompatibility endow engineered proteins with outstanding performance for disease therapy. Nevertheless, their stability is dramatically impaired in blood circulation, hindering clinical translations. Thus, many strategies have been developed to improve the stability, efficacy, bioavailability, and productivity of therapeutic proteins for clinical applications. In this review, we summarize the recent progress in the fabrication and application of therapeutic proteins. We first introduce various strategies for improving therapeutic efficacy via bioengineering and nanoassembly. Furthermore, we highlight their diverse applications as growth factors, nanovaccines, antibody-based drugs, bioimaging molecules, and cytokine receptor antagonists. Finally, a summary and perspective for the future development of therapeutic proteins are presented.