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[相关成果 ] 一种人工染色体及其构建方法和应用 进入全文
智慧芽
提供了一种人工染色体及其构建方法和应用。人工染色体包括连接的初始人工染色体和功能基因；功能基因包括Cas9基因、Ura筛选标记基因、gRNA识别序列、同源序列1和片段同源序列。构建方法：将功能基因通过酶切酶连的方式连接到初始人工染色体上；将连接产物转化至大肠杆菌中，并在氯霉素抗性平板上挑取阳性克隆。DNA大片段胞内组装：将上述人工染色体和待组装的DNA大片段导入酵母细胞中，通过胞内同源重组完成组装。还公开了上述人工染色体在基因克隆、DNA合成中的应用。本公开的人工染色体可提高大片段DNA合成效率，避免了体外操作易断裂，效率低的问题，为后续完整基因组的合成提供了工具。
[学术文献 ] Engineered extrachromosomal oncogene amplifications promote tumorigenesis 进入全文
nature
Focal gene amplifications are among the most common cancer-associated mutations1 but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs)2 in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures. We also apply this approach to generate mice harbouring Cre-inducible Myc- and Mdm2-containing ecDNAs analogous to those occurring in human cancers. We show that the engineered ecDNAs spontaneously accumulate in primary cells derived from these animals, promoting their proliferation, immortalization and transformation. Finally, we demonstrate the ability of Mdm2-containing ecDNAs to promote tumour formation in an autochthonous mouse model of hepatocellular carcinoma. These findings offer insights into the role of ecDNA-mediated gene amplifications in tumorigenesis. We anticipate that this approach will be valuable for investigating further unresolved aspects of ecDNA biology and for developing new preclinical immunocompetent mouse models of human cancers harbouring specific focal gene amplifications.
[科研项目 ] Gene Control Startup Concinnity Secures £3M Seed Funding to Advance Gene Therapy Safety 进入全文
Concinnity Genetics
Concinnity Genetics, an Edinburgh-based company specializing in gene control, has successfully completed an oversubscribed £3 million seed funding round. The funding was spearheaded by Eos Advisory, with contributions from Scottish Enterprise, Old College Capital (OCC)—the University of Edinburgh’s venture investment fund—and Maven Capital Partners. Co-founded by Jessica Birt and Dr. Matthew Dale, Concinnity aims to enhance the safety of gene therapies through innovative RNA-based control systems. Using a proprietary AI platform combined with synthetic biology expertise, these systems allow precise regulation of gene therapies post-administration, offering the ability to mitigate side effects dynamically.
[政策法规 ] Engineering Biology for Space Health: An Innovative Research Roadmap 进入全文
美国工程生物学研究联盟（EBRC）
The expansion of human capabilities in near Earth orbit and deep space will greatly promote scientific discoveries and technological progress, with far-reaching and extensive impacts. Through the rapid development of engineering biology, it is expected to further expand human spaceflight capabilities and promote technological innovation on Earth. In October 2024, the Engineering Biology for Space Health: An Innovative Research Roadmap, released by the Engineering Biology Research Consortium (EBRC), elaborated on the key breakthroughs and important milestones of engineering biology in the field of space health around three core themes: health and medicine, food and nutrition, and environmental control and life support. It proposed an innovative path for applying engineering biology to space health research to improve environmental control and life support systems, provide richer nutrition, and ensure the health and safety of crew members.
[学术文献 ] The Quest for the Sli Locus 进入全文
Potato Research
Genetic gain in potato breeding is limited by the heterozygous tetraploid genome of cultivated potato. Recent efforts to breed potato at the diploid level promise to improve genetic gain and allow more straightforward genetics and introgression breeding. Diploid F1 hybrid potato breeding relies on the ability to create diploid inbred lines via repeated self-fertilization. However, self-fertilization of diploid potato is hampered by a gametophytic self-incompatibility system encoded by the S-locus that prevents fertilization by self-pollen. Nonetheless, self-compatible diploid potato genotypes exist and have been used to create inbred lines. The S-locus inhibitor (Sli) gene is a dominant gene that provides strong self-compatibility in diploid potato and was previously mapped to Chromosome 12. While the Sli gene has already been identified and characterized, the most tedious challenge was to develop the optimal phenotyping methods and genetic populations preceding the cloning of this gene. To this end, we developed an effective phenotyping protocol to identify suitable parents and create diploid populations segregating for Sli. We show that an accurate phenotyping method is crucial to discriminate between confounding fertility factors and self-compatibility. In addition, we found that the Sli locus shows extreme segregation distortion on Chromosome 12. Finally, we used these insights to develop three F1 populations that segregate for Sli, which we later used for the identification of the Sli gene.
[学术文献 ] Identification, Elucidation and Deployment of a Cytoplasmic Male Sterility System for Hybrid Potato 进入全文
Biology
Conventional potato breeding has produced only limited genetic gain due to the polyploid nature of the crop. In recent years, hybrid potato breeding at the diploid level has been developed to overcome this limited genetic gain. In diploid potato breeding, homozygous inbred lines are developed by self-fertilization, enabling incremental improvements of the material in each generation. This type of breeding requires self-fertility, which makes hybridization of inbred lines labor-cumbersome and results in hybrids that produce many undesirable berries in the field. In many crop species, cytoplasmic male sterility is used to produce maternal inbred lines that are male sterile. In this study, we explore the antherless cytoplasmic male sterility system in potato. We identify a recessive locus that is required for sterility and we show that this trait is expressed in Phureja cytoplasm but not in Andigena or Tuberosum cytoplasm. We implemented this system in hybrid seed production and show that the resulting hybrids set far fewer berries in the field than male fertile controls.
