Trends in biotechnology最新文献

Biopharma start-ups drive pharmaceutical innovation, relying on local ecosystems that connect key actors, resources, and enabling factors. This article synthesizes literature and expert insights into a framework that outlines five pillars-networks, technology transfer, funding, education, and culture-to guide policymakers and stakeholders in building thriving biopharma clusters and accelerating innovation.

Clustered regularly interspaced short palindromic repeats (CRISPR)-based environmental biosurveillance (CRISPR-eBx) offers a portable, specific, sensitive, and cost-effective platform for detecting organisms from environmental nucleic acids. Applications are broad, ranging from pathogen detection to monitoring invasive and endangered species across a range of environmental sources, including water, soil, and air. However, if CRISPR-eBx is to be deployed for novel biological/gene targets and environmental sources, key challenges must be addressed. This review synthesizes recent developments at the intersection of CRISPR technology, computational science, synthetic biology, and biosurveillance. We highlight promising innovations and identify knowledge gaps to present a strategic road map for establishing CRISPR-eBx as a next-generation, frontline biosurveillance solution.

Membrane transporters play crucial roles in metabolite exchange, cellular communication, and metabolic homeostasis and are attractive targets in metabolic engineering for the development of microbial cell factories. While transporter engineering has proven effective in enhancing nutrient uptake, improving product secretion, and optimizing metabolic flux, its broader application is limited by incomplete knowledge of membrane transport systems and the sometimes high promiscuity of transporters, often resulting in unpredictable outcomes. This review provides an overview of recent progress in transporter engineering and characterization methods, highlighting their potential to enhance the production of bio-based chemicals.

Current cardiac cell models for drug screening often face a trade-off between cellular maturity and throughput. 3D human-induced pluripotent stem cell (hiPSC)-based heart models typically exhibit adult-like features, but their use often requires large cell numbers or complex equipment. In this study, we developed cost-effective methods to scale the production of stem cell-derived cardiac microtissues (cMTs) containing three cardiac cell types and assess calcium transients and action potential metrics for high-throughput screening (HTS). Automating the procedure revealed reproducible drug responsiveness and predictive accuracy in a reference compound screen. Furthermore, an arrhythmic phenotype was reliably triggered in cMTs containing cardiomyocytes with an RYR2 mutation. Screening a library of more than 2000 compounds demonstrated the suitability of the assay for identifying potential antiarrhythmic agents. Our findings underscore the scalability of cMTs and their utility in disease modeling and HTS. The advanced technology readiness level of cMTs supports their regulatory uptake and acceptance within the pharmaceutical industry.

Pharmaceutical pollution, defined as the presence of antibiotics, antidepressants, antidiabetics, and other pharmaceuticals in the environment, is a ubiquitous problem. Active pharmaceutical ingredients (APIs), along with their metabolites and excipients, pose a threat to public health, biodiversity, and ecosystems. In response to this environmental challenge, European legislation has been updated to include certain APIs as priority pollutants and to require the installation of advanced wastewater treatment facilities capable of eliminating them. To deliver an effective response to pharmaceutical pollution, we believe it is essential to implement a combination of at-source and end-of-pipe solutions. In addition, cutting-edge biotechnological tools such as gene engineering, omics analysis, biosensors, and microfluidics have yet to realize their full potential in tackling pharmaceutical pollution.

Personal genomics and gene editing raise the prospect of undetectable gene doping. Athletes' genome sequencing should be integrated into the Athlete Biological Passport to deter future abuse. This provocative vision calls for urgent debate on fairness in sport and for new solutions to share genomic data while preserving privacy.

The COVID-19 pandemic highlighted the urgent need for advanced lung regenerative medicine. While traditional research focused on biochemical pathways, biophysical cues are equally critical regulators of lung cell behavior. This review discusses the role of key mechanical cues including cyclic stretch, strain/pressure, geometry, and matrix stiffness on lung cells in health and disease. The focus is on the evaluation of biomimetic platforms (decellularized scaffolds, dynamic surfaces, biomaterial constructs, and lung-on-chip devices) that recapitulate these environments; and the paradigm shifts in the field which show the importance of physiologically relevant systems. Finally, we identify challenges and future directions for translating mechanobiology-informed approaches into clinical therapies, highlighting their transformative potential for lung tissue engineering.

A biofoundry integrates laboratory automation with Design-Build-Test-Learn (DBTL) workflows to accelerate strain development for sustainable manufacturing. Quantifying the economic efficiency of automated processes remains challenging. Here, we define the robot-assisted module (RAM) as a plug-and-play unit for constructing workflow and apply the Experiment Price Index (EPI), a standardized metric that combines time and cost per sample to evaluate and optimize synthetic biology workflows. Using EPI calculation and RAMs, we developed four workflows for strain development: guide (g)RNA cloning, genome editing, DNA assembly, and sample analysis. EPI identified workflow bottlenecks, elimination of redundancies, and assessment of techno-economic tradeoffs. We further extended the EPI framework on techno-economic assessment (TEA) by estimating return on investment (ROI) and payback periods for biofoundry operations at varying project scales. Our results demonstrate EPI for cost-effective experimental planning and scalable biofoundry deployment. Beyond strain engineering, EPI serves as a universal tool for evaluating automation efficiency across biotechnology.

Piezoelectric scaffolds are emerging as promising therapeutic strategies for musculoskeletal regeneration. These materials convert mechanical forces, ranging from intrinsic motion to focused ultrasound (US) force, into localized electrical cues for tissue-specific musculoskeletal regeneration. Mechanistically, piezoelectric-converted electrical energy activates mechanosensitive and voltage-gated channels that trigger early regenerative signaling pathways. In this review, we describe the fundamental principles of the piezoelectric material class that focus on dipole alignment, geometry, and activation paradigms to culminate in their differential effects on the regeneration of musculoskeletal tissues. We also discuss lead-free platforms, closed-loop systems, as well as printable constructs capable of delivering wire-free electrical stimulation (ES). Finally, we discuss current translational challenges and future directions and practical steps toward clinical adoption of piezoelectric scaffolds.

Engineering infrared light sensitivity in the blind human retina could restore visual function in patients with regional retinal degeneration. However, current approaches are complex and contain non-human biological components. Using rational protein design, we engineered human transient receptor potential vanilloid 1 (hTRPV1) channels (Δ786-840) with temperature sensitivity that shifted from 45 to 41°C, which enabled near-infrared (NIR) light-induced heat activation of mammalian cells at close to physiological temperatures. When expressed in ganglion cells of human retinal explants, Δ786-840 TRPV1 generated robust spiking responses to brief NIR light-induced temperature transients. In addition, increasing intensity of radiation evoked graded responses correlating with increasing firing frequencies. Unlike previous approaches, which used non-human TRPV1 channels, risking immune reactions, and a multicomponent system that poses barriers to clinical implementation, this single-component human-derived approach eliminates immunogenicity concerns, addressing a major challenge to clinical translation, and allows gene delivery using adeno-associated virus (AAV) vectors.