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Identification of non-canonical peptides with moPepGen 用moPepGen鉴定非规范肽
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02701-0
Chenghao Zhu, Lydia Y. Liu, Annie Ha, Takafumi N. Yamaguchi, Helen Zhu, Rupert Hugh-White, Julie Livingstone, Yash Patel, Thomas Kislinger, Paul C. Boutros
{"title":"Identification of non-canonical peptides with moPepGen","authors":"Chenghao Zhu, Lydia Y. Liu, Annie Ha, Takafumi N. Yamaguchi, Helen Zhu, Rupert Hugh-White, Julie Livingstone, Yash Patel, Thomas Kislinger, Paul C. Boutros","doi":"10.1038/s41587-025-02701-0","DOIUrl":"https://doi.org/10.1038/s41587-025-02701-0","url":null,"abstract":"<p>Proteogenomics is limited by the challenge of modeling the complexities of gene expression. We create moPepGen, a graph-based algorithm that comprehensively generates non-canonical peptides in linear time. moPepGen works with multiple technologies, in multiple species and on all types of genetic and transcriptomic data. In human cancer proteomes, it enumerates previously unobservable noncanonical peptides arising from germline and somatic genomic variants, noncoding open reading frames, RNA fusions and RNA circularization.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"272 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144296162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A laboratory-evolved CRISPR-associated transposase adapts to human cells 实验室进化的crispr相关转座酶适应于人类细胞
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02720-x
Iris Marchal
{"title":"A laboratory-evolved CRISPR-associated transposase adapts to human cells","authors":"Iris Marchal","doi":"10.1038/s41587-025-02720-x","DOIUrl":"https://doi.org/10.1038/s41587-025-02720-x","url":null,"abstract":"<p>CRISPR-associated transposases (CASTs) are an attractive candidate for genome editing applications, as they enable the insertion of large DNA cargoes without creating double-strand breaks. However, CAST systems have shown limited activity in human cells. In a paper published in <i>Science</i>, Witte et al. apply phage-assisted continuous evolution (PACE) to direct the rapid evolution of new CAST variants, acquiring a CAST system capable of efficiently integrating gene-size cargoes in human cells.</p><p>Iterative rounds of PACE yielded an evolved TnsB — a component of the Type I-F CAST transposition machinery — with integration efficiency in HEK cells more than 200-fold higher than that of the wild type. The evolved TnsB contained ten activity-enhancing mutations spanning multiple domains, suggesting that PACE optimized diverse functionalities to improve TnsB’s performance and that obtaining such a variant through rational protein engineering would have been unlikely. Notably, the evolved TnsB did not require supplementation with the accessory protein ClpX, a cytotoxic factor previously used to increase CAST editing efficiency.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"178 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Court reignites CRISPR patent dispute 法院重新点燃CRISPR专利之争
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02717-6
{"title":"Court reignites CRISPR patent dispute","authors":"","doi":"10.1038/s41587-025-02717-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02717-6","url":null,"abstract":"<p>The University of California and the University of Vienna have convinced a US appeals court to revive their bid for patent rights to the CRISPR–Cas9 gene-editing technology created by their scientists Jennifer Doudna and Emmanuelle Charpentier. The case was sent back to the Patent Office’s Patent Trial and Appeal Board for reconsideration after the court found fault with a previous patent tribunal’s ruling giving key CRISPR–Cas9 patent rights to the Broad Institute and researcher Feng Zhang. This will give Nobel prize winners Doudna and Charpentier and their respective universities another chance to claim rights to CRISPR–Cas9 patents as true inventors in the United States.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"13 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The New Clinical Investigation exclusivity: a substantial source of monopoly time for brand drugs 新的临床研究排他性：品牌药垄断时间的实质性来源
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02696-8
Robin Feldman, Gideon Schor, Ramy Alsaffar
{"title":"The New Clinical Investigation exclusivity: a substantial source of monopoly time for brand drugs","authors":"Robin Feldman, Gideon Schor, Ramy Alsaffar","doi":"10.1038/s41587-025-02696-8","DOIUrl":"https://doi.org/10.1038/s41587-025-02696-8","url":null,"abstract":"In the United States, some non-patent exclusivities can have an outsized impact on the ability of generic competitors to enter the market and lower drug prices.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"153 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CRISPR-TO directs RNA to defined intracellular locations CRISPR-TO将RNA引导到细胞内的特定位置
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02721-w
Iris Marchal
{"title":"CRISPR-TO directs RNA to defined intracellular locations","authors":"Iris Marchal","doi":"10.1038/s41587-025-02721-w","DOIUrl":"https://doi.org/10.1038/s41587-025-02721-w","url":null,"abstract":"<p>Although spatial RNA organization is central to cellular functions and disease mechanisms, its functional consequences remain poorly understood owing to a lack of tools for manipulating RNA localization within cells. Writing in <i>Nature</i>, Han et al. introduce CRISPR-mediated transcriptome organization (CRISPR-TO), a method that uses the RNA-guiding properties of nuclease-dead dCas13 to transport endogenous RNA to desired subcellular compartments. CRISPR-TO works via chemical-inducible dimerization and consists of three components: a dCas13 fused with one dimerization domain, a subcellular localization signal or motor protein fused with the other dimerization domain, and guide RNAs targeting the RNA of interest. The plant hormone ABA was selected as the inducer.</p><p>The authors tested CRISPR-TO by localizing various endogenous mRNAs to the outer mitochondrial membrane (OMM). They observed substantial OMM localization of the target mRNAs despite their varying expression levels. The use of three dCas13-binding sites on a target mRNA yielded 50.6% localization to the OMM.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"88 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biotech financing: divide and reset 生物技术融资：划分与重置
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02723-8
{"title":"Biotech financing: divide and reset","authors":"","doi":"10.1038/s41587-025-02723-8","DOIUrl":"https://doi.org/10.1038/s41587-025-02723-8","url":null,"abstract":"Today’s uniquely challenging biotech climate may result in a more resilient sector.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"23 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
FDA says GM pigs safe to eat FDA称转基因猪可以安全食用
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02716-7
{"title":"FDA says GM pigs safe to eat","authors":"","doi":"10.1038/s41587-025-02716-7","DOIUrl":"https://doi.org/10.1038/s41587-025-02716-7","url":null,"abstract":"<p>Pigs genetically modified to resist a devastating virus are now approved for human consumption in the United States. British animal genetics company Genus, based in Basingstoke, announced in April that the US Food and Drug Administration (FDA) had approved its gene-edited pigs after a lengthy review through the agency’s Investigational New Drug regulatory pathway.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"92 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biotech news from around the world 来自世界各地的生物技术新闻
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02714-9
{"title":"Biotech news from around the world","authors":"","doi":"10.1038/s41587-025-02714-9","DOIUrl":"https://doi.org/10.1038/s41587-025-02714-9","url":null,"abstract":"<p>A new law proposed by the Federal Council would ease restrictions on plants developed through new genomic techniques such as CRISPR. Currently in Switzerland, such plants are treated similarly to those developed through conventional genetic engineering, including an ongoing moratorium on cultivation. If passed, the Breeding Technologies Act would enact a risk-based authorization system that reflects the potential of new breeding technologies and the need for appropriate safeguards.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Organoids Organoids
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02698-6
{"title":"Organoids","authors":"","doi":"10.1038/s41587-025-02698-6","DOIUrl":"https://doi.org/10.1038/s41587-025-02698-6","url":null,"abstract":"Recent patents relating to the production, culture and use of organoids.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"229 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Infant receives the first customized CRISPR therapy 婴儿接受首个定制的CRISPR治疗
IF 46.9 1区 生物学
Nature biotechnology Pub Date : 2025-06-16 DOI: 10.1038/s41587-025-02719-4
Iris Marchal
{"title":"Infant receives the first customized CRISPR therapy","authors":"Iris Marchal","doi":"10.1038/s41587-025-02719-4","DOIUrl":"https://doi.org/10.1038/s41587-025-02719-4","url":null,"abstract":"<p>Base and prime editors promise to correct nearly all known pathogenic variants, but their therapeutic development is restricted to a handful of recurrent mutations owing to the high cost of bringing gene therapies to market. Writing in the <i>New England Journal of Medicine</i>, Musunuru et al. report on the rapid development of a customized base-editing therapy, provided to an infant born with a rare disease and delivered in vivo to hepatocytes through lipid nanoparticles.</p><p>The patient, who was diagnosed with a rare metabolic disease of the urea cycle known as carbamoyl phosphate synthetase 1 (CPS1) deficiency that prevents the proper breakdown of protein from food, received the first dose of base-editing therapy at just seven months of age. Within two months, the authors developed a cell line harboring two <i>CPS1</i> variants identified in the patient’s genome and screened various adenine base editors with guide RNAs tiling one of those <i>CPS1</i> variants. They selected the most efficient and precise base editor, called k-abe. Five months after birth, they assessed the in vivo efficiency of k-abe in a patient-specific mouse model, showing up to 42% whole-liver corrective editing. Safety studies in nonhuman primates and analyses of off-target editing in hepatocytes cleared the way for regulatory approval.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"35 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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