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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.
Palabras clave – provistas por la editorial

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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

Solid-phase capture and profiling of open chromatin by spatial ATAC

Enric Llorens-BobadillaORCID; Margherita ZamboniORCID; Maja MarklundORCID; Nayanika BhallaORCID; Xinsong ChenORCID; Johan HartmanORCID; Jonas Frisén; Patrik L. StåhlORCID

<jats:title>Abstract</jats:title><jats:p>Current methods for epigenomic profiling are limited in their ability to obtain genome-wide information with spatial resolution. We introduce spatial ATAC, a method that integrates transposase-accessible chromatin profiling in tissue sections with barcoded solid-phase capture to perform spatially resolved epigenomics. We show that spatial ATAC enables the discovery of the regulatory programs underlying spatial gene expression during mouse organogenesis, lineage differentiation and in human pathology.</jats:p>

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

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RNA recording in single bacterial cells using reprogrammed tracrRNAs

Chunlei JiaoORCID; Claas Reckstadt; Fabian KönigORCID; Christina HombergerORCID; Jiaqi YuORCID; Jörg VogelORCID; Alexander J. WestermannORCID; Cynthia M. SharmaORCID; Chase L. BeiselORCID

<jats:title>Abstract</jats:title><jats:p>Capturing an individual cell’s transcriptional history is a challenge exacerbated by the functional heterogeneity of cellular communities. Here, we leverage reprogrammed tracrRNAs (Rptrs) to record selected cellular transcripts as stored DNA edits in single living bacterial cells. Rptrs are designed to base pair with sensed transcripts, converting them into guide RNAs. The guide RNAs then direct a Cas9 base editor to target an introduced DNA target. The extent of base editing can then be read in the future by sequencing. We use this approach, called TIGER (transcribed RNAs inferred by genetically encoded records), to record heterologous and endogenous transcripts in individual bacterial cells. TIGER can quantify relative expression, distinguish single-nucleotide differences, record multiple transcripts simultaneously and read out single-cell phenomena. We further apply TIGER to record metabolic bet hedging and antibiotic resistance mobilization in <jats:italic>Escherichia coli</jats:italic> as well as host cell invasion by <jats:italic>Salmonella</jats:italic>. Through RNA recording, TIGER connects current cellular states with past transcriptional states to decipher complex cellular responses in single cells.</jats:p>

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

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Single-cell recording of cellular RNAs in bacteria

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

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Unidirectional single-file transport of full-length proteins through a nanopore

Luning YuORCID; Xinqi KangORCID; Fanjun Li; Behzad MehrafroozORCID; Amr MakhamrehORCID; Ali FallahiORCID; Joshua C. FosterORCID; Aleksei AksimentievORCID; Min ChenORCID; Meni WanunuORCID

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

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Programmable A-to-Y base editing by fusing an adenine base editor with an N-methylpurine DNA glycosylase

Huawei TongORCID; Xuchen Wang; Yuanhua Liu; Nana Liu; Yun Li; Jiamin Luo; Qian Ma; Danni Wu; Jiyong LiORCID; Chunlong XuORCID; Hui YangORCID

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

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Protein identification using a digestion-free nanopore approach

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

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Cell-type-specific prediction of 3D chromatin organization enables high-throughput in silico genetic screening

Jimin Tan; Nina Shenker-TaurisORCID; Javier Rodriguez-Hernaez; Eric Wang; Theodore Sakellaropoulos; Francesco BoccalatteORCID; Palaniraja Thandapani; Jane Skok; Iannis Aifantis; David Fenyö; Bo XiaORCID; Aristotelis TsirigosORCID

<jats:title>Abstract</jats:title><jats:p>Investigating how chromatin organization determines cell-type-specific gene expression remains challenging. Experimental methods for measuring three-dimensional chromatin organization, such as Hi-C, are costly and have technical limitations, restricting their broad application particularly in high-throughput genetic perturbations. We present C.Origami, a multimodal deep neural network that performs de novo prediction of cell-type-specific chromatin organization using DNA sequence and two cell-type-specific genomic features—CTCF binding and chromatin accessibility. C.Origami enables in silico experiments to examine the impact of genetic changes on chromatin interactions. We further developed an in silico genetic screening approach to assess how individual DNA elements may contribute to chromatin organization and to identify putative cell-type-specific <jats:italic>trans</jats:italic>-acting regulators that collectively determine chromatin architecture. Applying this approach to leukemia cells and normal T cells, we demonstrate that cell-type-specific in silico genetic screening, enabled by C.Origami, can be used to systematically discover novel chromatin regulation circuits in both normal and disease-related biological systems.</jats:p>

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

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Improved cytosine base editors generated from TadA variants

Dieter K. LamORCID; Patricia R. FelicianoORCID; Amena ArifORCID; Tanggis Bohnuud; Thomas P. Fernandez; Jason M. Gehrke; Phil GraysonORCID; Kin D. Lee; Manuel A. Ortega; Courtney Sawyer; Noah D. SchwaegerleORCID; Leila Peraro; Lauren Young; Seung-Joo Lee; Giuseppe CiaramellaORCID; Nicole M. GaudelliORCID

<jats:title>Abstract</jats:title><jats:p>Cytosine base editors (CBEs) enable programmable genomic C·G-to-T·A transition mutations and typically comprise a modified CRISPR–Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination. While improved CBEs that decrease stochastic genome-wide off-targets have subsequently been reported, these editors can suffer from suboptimal on-target performance. Here, we report the generation and characterization of CBEs that use engineered variants of TadA (CBE-T) that enable high on-target C·G to T·A across a sequence-diverse set of genomic loci, demonstrate robust activity in primary cells and cause no detectable elevation in genome-wide mutation. Additionally, we report cytosine and adenine base editors (CABEs) catalyzing both A-to-I and C-to-U editing (CABE-Ts). Together with ABEs, CBE-Ts and CABE-Ts enable the programmable installation of all transition mutations using laboratory-evolved TadA variants with improved properties relative to previously reported CBEs.</jats:p>

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

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Fresh from the biotech pipeline: fewer approvals, but biologics gain share

Melanie Senior

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

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Control of acute myeloid leukemia by a trifunctional NKp46-CD16a-NK cell engager targeting CD123

Laurent GauthierORCID; Angela Virone-OddosORCID; Jochen Beninga; Benjamin Rossi; Céline Nicolazzi; Céline Amara; Audrey Blanchard-Alvarez; Nicolas Gourdin; Jacqueline Courta; Alexandra Basset; Magali Agnel; Franceline Guillot; Gwendoline Grondin; Hélène BonnevauxORCID; Anne-Laure Bauchet; Ariane Morel; Yannis Morel; Marielle Chiron; Eric VivierORCID

<jats:title>Abstract</jats:title><jats:p>CD123, the alpha chain of the IL-3 receptor, is an attractive target for acute myeloid leukemia (AML) treatment. However, cytotoxic antibodies or T cell engagers targeting CD123 had insufficient efficacy or safety in clinical trials. We show that expression of CD64, the high-affinity receptor for human IgG, on AML blasts confers resistance to anti-CD123 antibody-dependent cell cytotoxicity (ADCC) in vitro. We engineer a trifunctional natural killer cell engager (NKCE) that targets CD123 on AML blasts and NKp46 and CD16a on NK cells (CD123-NKCE). CD123-NKCE has potent antitumor activity against primary AML blasts regardless of CD64 expression and induces NK cell activation and cytokine secretion only in the presence of AML cells. Its antitumor activity in a mouse CD123<jats:sup>+</jats:sup> tumor model exceeds that of the benchmark ADCC-enhanced antibody. In nonhuman primates, it had prolonged pharmacodynamic effects, depleting CD123<jats:sup>+</jats:sup> cells for more than 10 days with no signs of toxicity and very low inflammatory cytokine induction over a large dose range. These results support clinical development of CD123-NKCE.</jats:p>

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

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