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Nature Biotechnology

Resumen/Descripción – provisto por la editorial en inglés
Nature Biotechnology is a monthly journal covering the science and business of biotechnology. It publishes new concepts in technology/methodology of relevance to the biological, biomedical, agricultural and environmental sciences as well as covers the commercial, political, ethical, legal, and societal aspects of this research. The first function is fulfilled by the peer-reviewed research section, the second by the expository efforts in the front of the journal. We provide researchers with news about business; we provide the business community with news about research developments.
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Institución detectada Período Navegá Descargá Solicitá
No detectada desde jul. 2012 / hasta dic. 2023 Nature.com

Información

Tipo de recurso:

revistas

ISSN impreso

1087-0156

ISSN electrónico

1546-1696

Editor responsable

Springer Nature

País de edición

Reino Unido

Fecha de publicación

Tabla de contenidos

A universal deep-learning model for zinc finger design enables transcription factor reprogramming

David M. IchikawaORCID; Osama AbdinORCID; Nader Alerasool; Manjunatha KogenaruORCID; April L. MuellerORCID; Han WenORCID; David O. Giganti; Gregory W. GoldbergORCID; Samantha Adams; Jeffrey M. SpencerORCID; Rozita Razavi; Satra Nim; Hong Zheng; Courtney Gionco; Finnegan T. ClarkORCID; Alexey Strokach; Timothy R. HughesORCID; Timothee LionnetORCID; Mikko TaipaleORCID; Philip M. KimORCID; Marcus B. NoyesORCID

<jats:title>Abstract</jats:title><jats:p>Cys<jats:sub>2</jats:sub>His<jats:sub>2</jats:sub> zinc finger (ZF) domains engineered to bind specific target sequences in the genome provide an effective strategy for programmable regulation of gene expression, with many potential therapeutic applications. However, the structurally intricate engagement of ZF domains with DNA has made their design challenging. Here we describe the screening of 49 billion protein–DNA interactions and the development of a deep-learning model, ZFDesign, that solves ZF design for any genomic target. ZFDesign is a modern machine learning method that models global and target-specific differences induced by a range of library environments and specifically takes into account compatibility of neighboring fingers using a novel hierarchical transformer architecture. We demonstrate the versatility of designed ZFs as nucleases as well as activators and repressors by seamless reprogramming of human transcription factors. These factors could be used to upregulate an allele of haploinsufficiency, downregulate a gain-of-function mutation or test the consequence of regulation of a single gene as opposed to the many genes that a transcription factor would normally influence.</jats:p>

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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Hallucinating functional protein sequences

David BelangerORCID; Lucy J. ColwellORCID

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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Three-dimensional structured illumination microscopy with enhanced axial resolution

Xuesong LiORCID; Yicong WuORCID; Yijun Su; Ivan Rey-Suarez; Claudia Matthaeus; Taylor B. Updegrove; Zhuang Wei; Lixia Zhang; Hideki SasakiORCID; Yue LiORCID; Min GuoORCID; John P. Giannini; Harshad D. Vishwasrao; Jiji ChenORCID; Shih-Jong J. Lee; Lin Shao; Huafeng Liu; Kumaran S. Ramamurthi; Justin W. TaraskaORCID; Arpita Upadhyaya; Patrick La RiviereORCID; Hari Shroff

<jats:title>Abstract</jats:title><jats:p>The axial resolution of three-dimensional structured illumination microscopy (3D SIM) is limited to ∼300 nm. Here we present two distinct, complementary methods to improve axial resolution in 3D SIM with minimal or no modification to the optical system. We show that placing a mirror directly opposite the sample enables four-beam interference with higher spatial frequency content than 3D SIM illumination, offering near-isotropic imaging with ∼120-nm lateral and 160-nm axial resolution. We also developed a deep learning method achieving ∼120-nm isotropic resolution. This method can be combined with denoising to facilitate volumetric imaging spanning dozens of timepoints. We demonstrate the potential of these advances by imaging a variety of cellular samples, delineating the nanoscale distribution of vimentin and microtubule filaments, observing the relative positions of caveolar coat proteins and lysosomal markers and visualizing cytoskeletal dynamics within T cells in the early stages of immune synapse formation.</jats:p>

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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Spatial transcriptomics for profiling the tropism of viral vectors in tissues

Min J. Jang; Gerard M. Coughlin; Cameron R. Jackson; Xinhong ChenORCID; Miguel R. Chuapoco; Julia L. Vendemiatti; Alexander Z. WangORCID; Viviana GradinaruORCID

<jats:title>Abstract</jats:title><jats:p>A barrier to advancing engineered adeno-associated viral vectors (AAVs) for precision access to cell subtypes is a lack of high-throughput, high-resolution assays to characterize in vivo transduction profiles. In this study, we developed an ultrasensitive, sequential fluorescence in situ hybridization (USeqFISH) method for spatial transcriptomic profiling of endogenous and viral RNA with a short barcode in intact tissue volumes by integrating hydrogel-based tissue clearing, enhanced signal amplification and multiplexing using sequential labeling. Using USeqFISH, we investigated the transduction and cell subtype tropisms across mouse brain regions of six systemic AAVs, including AAV-PHP.AX, a new variant that transduces robustly and efficiently across neurons and astrocytes. Here we reveal distinct cell subtype biases of each AAV variant, including a bias of AAV-PHP.N toward excitatory neurons. USeqFISH also enables profiling of pooled regulatory cargos, as we show for a 13-variant pool of microRNA target sites in AAV genomes. Lastly, we demonstrate potential applications of USeqFISH for in situ AAV profiling and multimodal single-cell analysis in non-human primates.</jats:p>

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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CLASH enables large-scale parallel knock-in for cell engineering

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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Massively parallel knock-in engineering of human T cells

Xiaoyun DaiORCID; Jonathan J. ParkORCID; Yaying DuORCID; Zhenkun Na; Stanley Z. Lam; Ryan D. ChowORCID; Paul A. Renauer; Jianlei Gu; Shan XinORCID; Zhiyuan Chu; Cun Liao; Paul Clark; Hongyu ZhaoORCID; Sarah SlavoffORCID; Sidi ChenORCID

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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Spatial tropism profiling of AAV vectors by ultrasensitive sequential FISH in tissue

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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Delivering 3 billion doses of Comirnaty in 2021

Nicholas Warne; Margaret Ruesch; Pamela Siwik; Paul Mensah; John Ludwig; Michael Hripcsak; Ranga Godavarti; Andrew Prigodich; Mikael DolstenORCID

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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Drug pipeline 4Q22 — sticking around

John Hodgson

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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2022 – toughing out the trough

John Hodgson

Palabras clave: Biomedical Engineering; Molecular Medicine; Applied Microbiology and Biotechnology; Bioengineering; Biotechnology.

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