Galactose Oxidase Enables Modular Assembly of Conjugates from Native Antibodies with High Drug-to-Antibody Ratios

The potential of antibody conjugates with high drug loading in anticancer therapy has recently been highlighted by the approval of Trastuzumab deruxtecan and Sacituzumab govitecan. These biopharmaceutical approaches have spurred interest in bioconjugation strategies with high and defined degrees antibody-to-drug (DAR) ratios, in particular on native antibodies. Here we report a glycoengineering methodology to generate antibody drug conjugates with DAR of up to eight, by combining highly selective enzymatic galactosylation and oxidation with biorthogonal tandem Knoevenagel-Michael addition chemistry. This three step approach offers a selective route to conjugates from native antibodies with high drug loading, and thus illustrates how biocatalysis can be used for the generation of biopharmaceuticals using mild reaction conditions.

Anisotropic MOF-on-MOF Growth of Isostructural Multilayer Metal–Organic Framework Heterostructures

Isostructural MOFs with similar crystallographic parameter are easily available for MOF-on-MOF growth and possible to form core–shell structure by isotropic growth. However, due to well-matched cell lattice, selective growth in isostructural MOF heterostructures remains a great challenge for engineering atypical MOF heterostructures. Herein, an anisotropic MOF-on-MOF growth strategy was developed to structure a range of multilayer sandwich-like ZIF-L heterostructures via stacking isostructural ZIF-L-Zn and ZIF-L-Co alternately with three-, five-, seven-, and more layer structures. Moreover, these heterostructures with highly designable feature were fantastic precursors for fabricating derivatives with tunable magnetic and catalytic properties. Such strategy explores a novel way of achieving anisotropic MOF-on-MOF growth between isostructural MOFs and opens up new horizons for regulating the properties by MOF modular assembly in versatile functional nanocomposites.

Metamachines of pluripotent colloids

Machines enabled the Industrial Revolution and are central to modern technological progress: A machine’s parts transmit forces, motion, and energy to one another in a predetermined manner. Today’s engineering frontier, building artificial micromachines that emulate the biological machinery of living organisms, requires faithful assembly and energy consumption at the microscale. Here, we demonstrate the programmable assembly of active particles into autonomous metamachines using optical templates. Metamachines, or machines made of machines, are stable, mobile and autonomous architectures, whose dynamics stems from the geometry. We use the interplay between anisotropic force generation of the active colloids with the control of their orientation by local geometry. This allows autonomous reprogramming of active particles of the metamachines to achieve multiple functions. It permits the modular assembly of metamachines by fusion, reconfiguration of metamachines and, we anticipate, a shift in focus of self-assembly towards active matter and reprogrammable materials.

Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants by Modular, Tetravalent, Bi-paratopic Antibodies

Neutralizing antibodies (nAbs) that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (S-protein) are promising therapeutics for COVID-19. However, natural bivalent nAbs suffer from limited potency and are vulnerable to SARS-CoV-2 variants with mutated RBDs. We report a novel format that enables modular assembly of bi-paratopic, tetravalent nAbs with antigen-binding sites from two distinct nAbs. The diabody-Fc-Fab format consists of a central Fc with a bivalent diabody fused to its N-terminus and two Fabs fused to its C-terminus. The diabody and Fab modules do not interfere with each other, and thus, any diabody can be combined with any Fab in a facile manner. We engineered a diabody-Fc-Fab that contained the paratopes of two distinct nAbs derived from a phage-displayed library of synthetic Abs. The tetravalent nAb was purified in high yields with methods used to produce conventional IgGs, and it exhibited favorable biophysical characteristics comparable to those of approved therapeutic antibodies. The tetravalent nAb bound to the S-protein trimer at least 100-fold more tightly than the bivalent IgGs (apparent KD <1 pM). Most importantly, the tetravalent nAb exhibited extremely high potencies in neutralization assays across a panel of pseudoviruses representing seven natural SARS-CoV-2 variants (IC50 <5 ng/mL), including several that resisted IgGs and are known to evade approved IgG drugs. Taken together, our results showed that the tetravalent diabody-Fc-Fab is a robust, modular platform for rapid production of drug-grade nAbs with potencies and breadth of coverage that far exceed those of conventional bivalent IgGs.

A method to assess design complexity of modular automatic assembly system in design phase

Purpose To find the system with minimum investment and best quality performance that is capable of producing all of the product variants, assessing the complexity of designing assembly system at the early concept stage is an essential step, which helps and instructs a designer to create a product- and system-oriented assembly solution with the least complexity. The purpose of this paper is to propose a quantifying measurement of complexity in the design of a modular automated assembly system. Design/methodology/approach The configurable assembly system is becoming a trend, which enables companies to quickly respond to changes caused by different product variants but without a large investment. One of the enabling factors is the availability of modular solutions of assembly modules that can be configured according to different technical requirements. This paper develops a methodology using fuzzy evaluation to calculate the design complexity in the design phase for a modular automatic assembly system. Fuzzy linguistic variables are used to measure the interaction among the influence factors, to deal with the uncertainty of the judgement. The proposed method investigates three matrices to present how the function-based assembly modules, design complexity factors, part attributes and product components, which are regarded as the main influence factors, complicate the construction of a modular assembly system. The design complexity is derived and quantified based on these assessments. Findings The proposed approach presents a formal quantification to evaluate the design complexity with regard to a modular assembly system from beginning, which can be identified and used as criteria to indicate the quality of performance and investment cost in advance. A mathematical model based on the fuzzy logic is established to provide both theoretical and practical guidance for the paper. To validate the predictive model, the statistic relationships between the assessed system design complexity, real assembly defect rate and investment cost are estimated based on regression analysis. The application of the presented methodology is demonstrated with regard to a traditional rear drive unit in the automotive industry. Originality/value This paper presents a developed method, which addresses the measures of complexity found in the design of a modular assembly system. It would help to run the design process with better resource allocation and cost estimation in a quantitative approach.

Magnetically tightened form-stable phase change materials with modular assembly and geometric conformality features

Recently, phase change materials (PCMs) have attracted significant attention due to their promising applications in many fields like solar energy and chip cooling. However, the present PCMs seriously suffer inevitable leakage and low thermal conduction. Magnetism can produce invisible field effects in the surrounding space. If there exist magnetic particles within this region, the effects will act on them emerging various fascinating phenomena. Inspired by this, we introduce hard magnetic particles (which can keep the effect after removing the magnetic field) to PCMs synthesizing an unprecedented magnetically tightened form-stable PCMs (MTPCMs), achieving multifunctions of leakage-proof, dynamic assembly and morphological reconfiguration, superior high thermal (increasing of 1400%~1600%) and electrical (>104 S/m) conductivity, and prominent compressive strength. Novel free-standing temperature control and high-performance thermal and electric conversion systems based on MTPCMs are furthermore developed. This work is a significant step toward exploiting a smart PCM for electronics and low-temperature energy storage.