Trends in biotechnology最新文献

Fossil fuel use drives greenhouse gas emissions and climate change, highlighting the need for alternatives like biomass-derived syngas. Syngas, mainly H₂ and CO, is produced via biomass gasification and offers a solution to environmental challenges. Syngas fermentation through the Wood-Ljungdahl pathway yields valuable chemicals under mild conditions. However, challenges in scaling up persist due to issues like unpredictable syngas composition and microbial fermentation contamination. This review covers advancements in genetic tools and metabolic engineering to expand product range, highlighting crucial enabling technologies that expedite strain development for acetogens and other non-model organisms. This review paper provides an in-depth exploration of syngas fermentation, covering microorganisms, gas composition effects, separation techniques, techno economic analysis, and commercialization efforts.

The adverse effects of academic bullying and harassment, which are longstanding issues within academic environments, on industry sectors have been inadequately addressed. This commentary explores the detrimental impacts of bullying and harassment in the biotech and biomedical engineering industries, including reduced employee morale, increased turnover, impaired collaboration, and hindered innovation.

A roadmap for medical device innovators is presented that highlights the essential steps for regulatory authorization, market access, and reimbursement strategies in the USA, with a focus on strategic planning for commercial success, underscoring the integration of regulatory and market access considerations from the initial development of a medical device.

Genome editing is highly valuable in biomedical research. Despite their versatility, current Prime editing (PE) techniques are limited to short sequence alterations [up to ~44 base pairs (bp)], and exhibit inconsistent or low efficiency across genomic loci, particularly when faced with poly-T sequences. To address these challenges, we developed an extended PE (exPE) technique that can potentially execute any precise genome editing. By harnessing RNA polymerase II (Pol II) promoters to transcribe extended PE guide RNAs (expegRNAs), exPE substantially improves editing efficiency and overcomes the challenges posed by poly-T sequences. Compared with conventional PE, exPE achieves up to a 14-fold increase in the efficiency of base conversions and short insertions, and, remarkably, up to a 259-fold improvement in regions with poly-T sequences. Uniquely, exPE enables seamless insertion of gene-sized DNA fragments into genomes, potentially correcting nearly 90% of human genetic variants, thereby broadening its applications in genetic research and therapy.

Efficient phage production has always been an urgent need in fields such as drug discovery, disease treatment, and gene evolution. To meet this demand, we constructed a robust cell-free synthesis system for generating M13 phage by simplifying its genome, enabling a three-times faster efficiency compared with the traditional method in vivo. We further developed a cell-free directed evolution system in droplets, comprising a modified helper plasmid (ΔPS-ΔgIII-ΔgVI) and the simplified M13 genome-carrying gene mutation library. This system was greatly improved when coupled with fluorescence-activated droplet sorting (FADS). We successfully evolved the T7 RNA polymerase (RNAP), achieving a twofold higher activity to read through the T7 terminator. Moreover, we evolved the tryptophan tRNA into a suppressor tRNA with an eightfold increase in activity to read through the stop codon UAG.

CRISPR/Cas-based diagnostics (CRISPR-Dx) face challenges, including difficulty in detecting ultrashort nucleotides, preamplification dependency, cross-contamination, insufficiency in on-pot detection paradigms, and inconvenience in detecting non-nucleic acid targets. This forum outlines the advances in engineered CRISPR RNA (crRNA) that address the aforementioned problems, highlighting challenges, opportunities, and future directions.

The Streptomyces chassis serves as an important platform for efficient biomanufacture of diverse secondary metabolite (SM) compounds, but the current chassis lacks compatibility for integration of these SM biosynthetic pathways reliably and consistently. This forum discusses harnessing naturally evolved multifaceted switches to reprogram the Streptomyces chassis for biomanufacturing applications.

Macrophage immune cells exist on a plastic spectrum of phenotypes governed by their physical and biochemical environment. Controlling macrophage function to facilitate immunological regeneration or fighting pathology has emerged as a therapeutic possibility. The rate-limiting step in translating macrophage immunomodulation therapies has been the absence of fundamental knowledge of how physics and biochemistry in the macrophage microenvironment converge to inform phenotype. In this review we explore recent trends in bioengineered model systems that integrate physical and biochemical variables applied to macrophage mechanosensing and plasticity. We focus on how tuning of mechanical forces and biomaterial composition orchestrate macrophage function in physiological and pathological contexts. Ultimately, a broader understanding of stimuli-responsiveness in macrophages leads to informed design for future modulatory therapies.

Cell-based therapies are revolutionizing medicine by replacing or modifying dysfunctional cells with healthy cells or engineered derivatives, offering disease reversal and cure. One promising approach is using cell-derived extracellular vesicles (EVs), which offer therapeutic benefits similar to cell transplants without the biosafety risks. Although EV applications face challenges like limited production, inadequate therapeutic loading, and poor targeting efficiency, recent advances in bioengineering have enhanced their effectiveness. Herein, we summarize technological breakthroughs in EV bioengineering over the past 5 years, highlighting their improved therapeutic functionalities and potential clinical prospects. We also discuss biomanufacturing processes, regulation, and safety considerations for bioengineered EV therapies, emphasizing the significance of establishing robust frameworks to ensure translation capability, safety, and therapeutic effectiveness for successful clinical adoption.

The demand for novel, minimally invasive, cost-effective, and easily readable diagnostic tools, primarily designed for the longitudinal monitoring of diseases and their treatments, has promoted the development of diagnostic systems that selectively target cells, tissues, or organs, at the same time minimizing their nonspecific accumulation, thus reducing the risk of toxicity and side effects. In this review, we explore the development of renal-clearable systems in non-invasive or minimally invasive detection protocols, all with the objective of minimizing nonspecific accumulation and its associated toxicity effects through quick renal excretion. These probes can identify molecules of interest or different healthy states of the patients through the direct analysis of urine (urinalysis). As we discuss, these diagnostics systems hold significant treatment monitoring potential.