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[前沿资讯 ] Protein design and optimization for synthetic cells 进入全文
Nature Reviews Bioengineering
Proteins are essential components in synthetic biology, providing multiple functions at the nanoscale. Newly developed protein optimization and design tools allow the generation of proteins with desired properties, offering new opportunities for the engineering of protein-based biological systems. In this Review, we explore how bottom-up synthetic biology, with its aim to construct synthetic cells, can use these tools to devise complex biological functions and functional systems from scratch. We provide an overview of current capabilities in protein optimization, de novo protein design and iterative system optimization, and discuss their potential in synthetic cell science with regard to standardization, the generation of missing functionality and integration. We conclude with the outline of an integrated pipeline that combines protein engineering, automated synthetic cell generation and active learning, which might allow the design of entirely new biological systems that do not rely on naturally evolved protein components.
[前沿资讯 ] Programmable gene insertion in human cells with a laboratory-evolved CRISPR-associated transposase 进入全文
science
The ability to install large DNA sequences into specified locations in the human genome has far-reaching implications, including paving the way for single-drug treatments of mutationally diverse loss-of-function genetic diseases. CRISPR-associated transposases (CASTs) are naturally occurring systems that support RNA-programmable insertion of gene-sized DNA but have shown minimal activity in human cells. Witte et al. developed a continuous evolution platform to improve CAST activity, yielding an evolved CAST with more than 200-fold increased activity in human cells. This enzyme enables efficient gene integration across a variety of therapeutically relevant genomic sites in multiple human cell types, representing a versatile new platform for mammalian cell genome editing.
[前沿资讯 ] Leaving synthetic pesticides behind 进入全文
science
"Mitigating pesticide effects will require multiple approaches. Chemical pesticides should be progressively replaced with agroecological measures such as invertebrate biological control agents and biopesticides, many of which are cost-effective, environmentally sound, and practicable (5). Preventative pest management without chemical pesticides can include planting pest-tolerant varieties (6); using light, pheromone, or sticky traps (7); removing pest resources, such as harvest residues and alternative host plants; and altering sowing dates (8). Other strategies include diversifying crops through intercropping or cover cropping; mulching or organic manuring; establishing flower strips that provide food for predators and parasitic wasps; and raising aquatic animals, such as fish, ducks, or frogs, in cropping fields, where they can prey on insect herbivores or weeds (9). Precision agriculture and digital tools could also decrease pesticide use. Robotics, unmanned aerial vehicles (UAVs), artificial intelligence–based computer vision, and data-driven forecasting or advisory systems can all enable timely, targeted interventions (10). Tractor-pulled or autonomous camera–equipped mechanical weeders, for instance, can surgically remove weeds from a standing crop, and UAVs can “precision-drop” natural enemies or deliver biopesticide patch sprays on infestation hotspots. However, the funds and training required to use such technologies limit their accessibility and impact."
[前沿资讯 ] 罗氏制药中国宣布投资20.4亿人民币在上海新建生物制药生产基地 进入全文
上海市人民政府外事办公室
5月8日，罗氏制药中国宣布投资20.4亿元人民币，用于在上海新建生物制药生产基地。当天投资项目启动仪式举行。作为上海市市长国际企业家咨询会议成员企业之一，罗氏此次加码投资旨在通过强化企业在华供应链和本地化生产布局，全面强化端到端的完整医药价值产业链，再次彰显了全球头部企业继续深耕中国市场、融入上海建设发展的长期承诺。 新项目用地约53亩，建筑面积约2万5千平方米，位于上海浦东新区张江高科技园区。该项目预计将于2029年正式落成，2031年正式投产。罗氏将可持续发展理念贯彻于新基地的建设和运营之中。新生产基地的建设将采用国际领先的生产工艺、100%采用绿色电力。该基地将用于罗视佳®（法瑞西单抗注射液）的本地化生产，不断满足中国患者对于创新疗法的需求。 全新生物制药生产基地建成后，将成为罗氏制药在中国的第二个创新药物生产基地，与位于百米之外的罗氏制药中国区总部现有生产基地协同运作，共同为中国患者提供创新药品。早在1994年，罗氏作为第一家跨国药企入驻浦东张江。1997年，罗氏在上海总部园区的生产车间正式建成投产，并于2005年在华建成了高致敏生产车间。20年来，这一生产基地严格遵循GMP规范，确保生产环境的严格控制，加速满足中国患者对高质量药品的需求。2024年，罗氏实现了抗流感创新药速福达®（玛巴洛沙韦）的本地化生产，快速应对流感高发季中国流感患者的需求。
[学术文献 ] Chromatin loops are an ancestral hallmark of the animal regulatory genome 进入全文
Nature
In bilaterian animals, gene regulation is shaped by a combination of linear and spatial regulatory information. Regulatory elements along the genome are integrated into gene regulatory landscapes through chromatin compartmentalization1,2, insulation of neighbouring genomic regions3,4 and chromatin looping that brings together distal cis-regulatory sequences5. However, the evolution of these regulatory features is unknown because the three-dimensional genome architecture of most animal lineages remains unexplored6,7. To trace the evolutionary origins of animal genome regulation, here we characterized the physical organization of the genome in non-bilaterian animals (sponges, ctenophores, placozoans and cnidarians)8,9 and their closest unicellular relatives (ichthyosporeans, filastereans and choanoflagellates)10 by combining high-resolution chromosome conformation capture11,12 with epigenomic marks and gene expression data. Our comparative analysis showed that chromatin looping is a conserved feature of genome architecture in ctenophores, placozoans and cnidarians. These sequence-determined distal contacts involve both promoter–enhancer and promoter–promoter interactions. By contrast, chromatin loops are absent in the unicellular relatives of animals. Our findings indicate that spatial genome regulation emerged early in animal evolution. This evolutionary innovation introduced regulatory complexity, ultimately facilitating the diversification of animal developmental programmes and cell type repertoires.
[学术文献 ] Bioremediation of complex organic pollutants by engineered Vibrio natriegens 进入全文
Nature
Industrial wastewater, petroleum pollution and plastic contamination are significant threats to global marine biosecurity because of their toxic, mutagenic and persistent nature1. The use of microorganisms in bioremediation has been constrained by the complexity of organic pollutants and limited tolerance to saline stress2. In this study, we used synthetic biology to engineer Vibrio natriegens into a strain capable of bioremediating complex organic pollutants in saline wastewater and soils. The competence master regulator gene tfoX was inserted into chromosome 1 of the V. natriegens strain Vmax and overexpressed to enhance DNA uptake and integration. Degradation gene clusters were chemically synthesized and assembled in yeast. We developed a genome engineering method (iterative natural transformation based on Vmax with amplified tfoX effect) to transfer five gene clusters (43 kb total) into Vmax. The engineered strain has the ability to bioremediate five organic pollutants (biphenyl, phenol, naphthalene, dibenzofuran and toluene) covering a broad substrate range, from monocyclic to multicyclic compounds, in industrial wastewater samples from a chlor–alkali plant and a petroleum refinery.
