{"title":"Cancer vaccines","authors":"","doi":"10.1038/s41587-024-02521-8","DOIUrl":"10.1038/s41587-024-02521-8","url":null,"abstract":"Recent patents relating to compositions and methods for producing and using cancer vaccines.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"29-29"},"PeriodicalIF":33.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989342","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}
Lisa Larrimore Ouellette, Victoria Fang, Nicholas T. Ouellette
{"title":"How will AI affect patent disclosures?","authors":"Lisa Larrimore Ouellette, Victoria Fang, Nicholas T. Ouellette","doi":"10.1038/s41587-024-02515-6","DOIUrl":"10.1038/s41587-024-02515-6","url":null,"abstract":"Artificial intelligence tools for drafting patents will exacerbate challenges with the disclosure of useful technical information in patent documents.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"26-28"},"PeriodicalIF":33.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02515-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy","authors":"Feifei Zhang, Ryan D. Chow, Emily He, Chuanpeng Dong, Shan Xin, Daniyal Mirza, Yanzhi Feng, Xiaolong Tian, Nipun Verma, Medha Majety, Yueqi Zhang, Guangchuan Wang, Sidi Chen","doi":"10.1038/s41587-024-02535-2","DOIUrl":"https://doi.org/10.1038/s41587-024-02535-2","url":null,"abstract":"<p>The complex nature of the immunosuppressive tumor microenvironment (TME) requires multi-agent combinations for optimal immunotherapy. Here we describe multiplex universal combinatorial immunotherapy via gene silencing (MUCIG), which uses CRISPR–Cas13d to silence multiple endogenous immunosuppressive genes in the TME, promoting TME remodeling and enhancing antitumor immunity. MUCIG vectors targeting four genes delivered by adeno-associated virus (AAV) (<i>Cd274</i>/<i>Pdl1</i>, <i>Lgals9</i>/<i>Galectin9</i>, <i>Lgals3</i>/<i>Galectin3</i> and <i>Cd47</i>; AAV-Cas13d-PGGC) demonstrate significant antitumor efficacy across multiple syngeneic tumor models, remodeling the TME by increasing CD8<sup>+</sup> T-cell infiltration while reducing neutrophils. Whole transcriptome profiling validates the on-target knockdown of the four target genes and shows limited potential off-target or downstream gene alterations. AAV-Cas13d-PGGC outperforms corresponding shRNA treatments and individual gene knockdown. We further optimize MUCIG by employing high-fidelity Cas13d (hfCas13d), which similarly showed potent gene silencing and in vivo antitumor efficacy, without weight loss or liver toxicity. MUCIG represents a universal method to silence multiple immune genes in vivo in a programmable manner, offering broad efficacy across multiple tumor types.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"20 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986817","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}
Jie Luo, Muge Molbay, Ying Chen, Izabela Horvath, Karoline Kadletz, Benjamin Kick, Shan Zhao, Rami Al-Maskari, Inderjeet Singh, Mayar Ali, Harsharan Singh Bhatia, David-Paul Minde, Moritz Negwer, Luciano Hoeher, Gian Marco Calandra, Bernhard Groschup, Jinpeng Su, Ceren Kimna, Zhouyi Rong, Nikolas Galensowske, Mihail Ivilinov Todorov, Denise Jeridi, Tzu-Lun Ohn, Stefan Roth, Alba Simats, Vikramjeet Singh, Igor Khalin, Chenchen Pan, Bernardo A. Arús, Oliver T. Bruns, Reinhard Zeidler, Arthur Liesz, Ulrike Protzer, Nikolaus Plesnila, Siegfried Ussar, Farida Hellal, Johannes Paetzold, Markus Elsner, Hendrik Dietz, Ali Erturk
{"title":"Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning","authors":"Jie Luo, Muge Molbay, Ying Chen, Izabela Horvath, Karoline Kadletz, Benjamin Kick, Shan Zhao, Rami Al-Maskari, Inderjeet Singh, Mayar Ali, Harsharan Singh Bhatia, David-Paul Minde, Moritz Negwer, Luciano Hoeher, Gian Marco Calandra, Bernhard Groschup, Jinpeng Su, Ceren Kimna, Zhouyi Rong, Nikolas Galensowske, Mihail Ivilinov Todorov, Denise Jeridi, Tzu-Lun Ohn, Stefan Roth, Alba Simats, Vikramjeet Singh, Igor Khalin, Chenchen Pan, Bernardo A. Arús, Oliver T. Bruns, Reinhard Zeidler, Arthur Liesz, Ulrike Protzer, Nikolaus Plesnila, Siegfried Ussar, Farida Hellal, Johannes Paetzold, Markus Elsner, Hendrik Dietz, Ali Erturk","doi":"10.1038/s41587-024-02528-1","DOIUrl":"https://doi.org/10.1038/s41587-024-02528-1","url":null,"abstract":"<p>Efficient and accurate nanocarrier development for targeted drug delivery is hindered by a lack of methods to analyze its cell-level biodistribution across whole organisms. Here we present Single Cell Precision Nanocarrier Identification (SCP-Nano), an integrated experimental and deep learning pipeline to comprehensively quantify the targeting of nanocarriers throughout the whole mouse body at single-cell resolution. SCP-Nano reveals the tissue distribution patterns of lipid nanoparticles (LNPs) after different injection routes at doses as low as 0.0005 mg kg<sup>−1</sup>—far below the detection limits of conventional whole body imaging techniques. We demonstrate that intramuscularly injected LNPs carrying SARS-CoV-2 spike mRNA reach heart tissue, leading to proteome changes, suggesting immune activation and blood vessel damage. SCP-Nano generalizes to various types of nanocarriers, including liposomes, polyplexes, DNA origami and adeno-associated viruses (AAVs), revealing that an AAV2 variant transduces adipocytes throughout the body. SCP-Nano enables comprehensive three-dimensional mapping of nanocarrier distribution throughout mouse bodies with high sensitivity and should accelerate the development of precise and safe nanocarrier-based therapeutics.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"36 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974844","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}
{"title":"Publisher Correction: Engineered platelets as targeted protein degraders and application to breast cancer models","authors":"Yu Chen, Samira Pal, Wen Li, Fengyuan Liu, Sichen Yuan, Quanyin Hu","doi":"10.1038/s41587-025-02559-2","DOIUrl":"https://doi.org/10.1038/s41587-025-02559-2","url":null,"abstract":"<p>Correction to: <i>Nature Biotechnology</i> https://doi.org/10.1038/s41587-024-02494-8, published online 3 December 2024.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"7 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968375","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}
{"title":"Agriculture to flourish on precision breeding: who will benefit?","authors":"Cormac Sheridan","doi":"10.1038/s41587-024-02532-5","DOIUrl":"10.1038/s41587-024-02532-5","url":null,"abstract":"From corn to bananas, farmers stand to gain from cultivating edited crops that are resilient and sustainable, paired with precision insecticides and microbe engineering. But reaching those with the greatest need remains a challenge.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"6-8"},"PeriodicalIF":33.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02532-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A cure for HIV? TCR agents seek to wipe out viral reservoirs","authors":"Monica Hoyos-Flight","doi":"10.1038/s41587-024-02529-0","DOIUrl":"10.1038/s41587-024-02529-0","url":null,"abstract":"Bispecific T cell receptor molecules designed to wipe out HIV-infected T cells offer glimpses of a cure.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"3-5"},"PeriodicalIF":33.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02529-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Making space for spatial biology in the clinic","authors":"","doi":"10.1038/s41587-024-02543-2","DOIUrl":"10.1038/s41587-024-02543-2","url":null,"abstract":"Spatial transcriptomics methods have been slow to move into clinical practice, but spatial proteomics are cheaper and more scalable, and could progress faster.","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"43 1","pages":"1-2"},"PeriodicalIF":33.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41587-024-02543-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maima Matin, Dalibor Hrg, Olena Litvinova, Małgorzata Łysek-Gładysinska, Agnieszka Wierzbicka, Jarosław Olav Horbańczuk, Artur Jóźwik, Atanas G. Atanasov
{"title":"Publisher Correction: The global patent landscape of functional food innovation","authors":"Maima Matin, Dalibor Hrg, Olena Litvinova, Małgorzata Łysek-Gładysinska, Agnieszka Wierzbicka, Jarosław Olav Horbańczuk, Artur Jóźwik, Atanas G. Atanasov","doi":"10.1038/s41587-024-02544-1","DOIUrl":"https://doi.org/10.1038/s41587-024-02544-1","url":null,"abstract":"<p>Correction to: <i>Nature Biotechnology</i> https://doi.org/10.1038/s41587-024-02410-0, published online 14 October 2024.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"28 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924907","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}
Gonzalo Benegas, Carlos Albors, Alan J. Aw, Chengzhong Ye, Yun S. Song
{"title":"A DNA language model based on multispecies alignment predicts the effects of genome-wide variants","authors":"Gonzalo Benegas, Carlos Albors, Alan J. Aw, Chengzhong Ye, Yun S. Song","doi":"10.1038/s41587-024-02511-w","DOIUrl":"https://doi.org/10.1038/s41587-024-02511-w","url":null,"abstract":"<p>Protein language models have demonstrated remarkable performance in predicting the effects of missense variants but DNA language models have not yet shown a competitive edge for complex genomes such as that of humans. This limitation is particularly evident when dealing with the vast complexity of noncoding regions that comprise approximately 98% of the human genome. To tackle this challenge, we introduce GPN-MSA (genomic pretrained network with multiple-sequence alignment), a framework that leverages whole-genome alignments across multiple species while taking only a few hours to train. Across several benchmarks on clinical databases (ClinVar, COSMIC and OMIM), experimental functional assays (deep mutational scanning and DepMap) and population genomic data (gnomAD), our model for the human genome achieves outstanding performance on deleteriousness prediction for both coding and noncoding variants. We provide precomputed scores for all ~9 billion possible single-nucleotide variants in the human genome. We anticipate that our advances in genome-wide variant effect prediction will enable more accurate rare disease diagnosis and improve rare variant burden testing.</p>","PeriodicalId":19084,"journal":{"name":"Nature biotechnology","volume":"14 1","pages":""},"PeriodicalIF":46.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911936","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}