Abstract：
:The exocrine pancreas, liver, and submandibular glands of the rat were used to express and secrete two exogenous, human protein hormones (growth hormone and insulin) into blood at physiological concentrations. Transfection, expression, and secretion were achieved by the in vivo retrograde injection of plasmid DNA into the secretory ducts of these glands. Pancreatic acinar cells secreted physiological concentrations of growth hormone into the circulation, and its secretion was enhanced by cholinergic stimulation. A human insulin gene was engineered to allow normal processing of insulin in non-beta cells. With this gene, the secretion of human insulin by the exocrine pancreas normalized elevated blood glucose levels in diabetic rats. These in vivo observations demonstrate the utility of retrograde ductal administration of naked DNA into exocrine organs as a novel method for the regulated systemic delivery of protein-based pharmaceuticals.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Goldfine ID,German MS,Tseng HC,Wang J,Bolaffi JL,Chen JW,Olson DC,Rothman SSdoi
10.1038/nbt1297-1378subject
Has Abstractpub_date
1997-12-01 00:00:00pages
1378-82issue
13eissn
1087-0156issn
1546-1696journal_volume
15pub_type
杂志文章abstract：:The construction of synthetic cell-cell communication networks can improve our quantitative understanding of naturally occurring signaling pathways and enhance our capabilities to engineer coordinated cellular behavior in cell populations. Towards accomplishing these goals in eukaryotes, we developed and analyzed two ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1162
更新日期：2005-12-01 00:00:00
abstract：:Whole-genome mRNA quantitation can be used to identify the genes that are most responsive to environmental or genotypic change. By searching for mutually similar DNA elements among the upstream non-coding DNA sequences of these genes, we can identify candidate regulatory motifs and corresponding candidate sets of core...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1098-939
更新日期：1998-10-01 00:00:00
abstract：:We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing laboratories and fed either a ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3353
更新日期：2015-10-01 00:00:00
abstract：:Current base editors (BEs) catalyze only base transitions (C to T and A to G) and cannot produce base transversions. Here we present BEs that cause C-to-A transversions in Escherichia coli and C-to-G transversions in mammalian cells. These glycosylase base editors (GBEs) consist of a Cas9 nickase, a cytidine deaminase...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-020-0592-2
更新日期：2021-01-01 00:00:00
abstract：:Transcriptional silencing, one of the major impediments to gene therapy in humans, is often accompanied by replication during late S-phase. We report that transcriptional silencing and late replication were prevented by DNA sequences that can initiate DNA replication (replicators). When replicators were included in si...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1202
更新日期：2006-05-01 00:00:00
abstract：:Mycobacterium tuberculosis is a natural mutant in oxyR, a close homolog of the central regulator of peroxide stress response in enteric bacteria. Inactivation of oxyR is specific for M. tuberculosis and other members of the M. tuberculosis complex. This phenomenon appears as a paradox due to the ability of this organi...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1196-1557
更新日期：1996-11-01 00:00:00
abstract：:Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-019-0322-9
更新日期：2020-02-01 00:00:00
abstract：:The advent of in vitro DNA amplification has enabled rapid acquisition of genomic information. We present here an analogous technique for protein detection, in which the coordinated and proximal binding of a target protein by two DNA aptamers promotes ligation of oligonucleotides linked to each aptamer affinity probe....
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0502-473
更新日期：2002-05-01 00:00:00
abstract：:Can new approaches for deriving human stem cells circumnavigate existing patents that dominate embryonic stem cell intellectual property? ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt0406-411
更新日期：2006-04-01 00:00:00
abstract：:The oncofetal fibronectin (B-FN) isoform is present in vessels of neoplastic tissues during angiogenesis but not in mature vessels. B-FN could therefore provide a target for diagnostic imaging and therapy of cancer. Phage display libraries have been used to isolate human antibody fragments with pan-species recognition...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1197-1271
更新日期：1997-11-01 00:00:00
abstract：:RNA-guided gene drives capable of spreading genomic alterations made in laboratory organisms through wild populations could be used to address environmental and public health problems. However, the possibility of unintended genome editing occurring through the escape of strains from laboratories, coupled with the pros...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3412
更新日期：2015-12-01 00:00:00
abstract：:Current DNA methylation assays are limited in the flexibility and efficiency of characterizing a large number of genomic targets. We report a method to specifically capture an arbitrary subset of genomic targets for single-molecule bisulfite sequencing for digital quantification of DNA methylation at single-nucleotide...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.1530
更新日期：2009-04-01 00:00:00
abstract：:Academic researchers have regularly ignored patents on key technologies as a strategy to maneuver around patent thickets and freedom-to-operate issues, but they may be more at risk than they realize. ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1107-1225
更新日期：2007-11-01 00:00:00
abstract：:The discovery of large multiprotein complexes in cells has increased the demand for improved heterologous protein production techniques to study their molecular structure and function. Here we describe MultiBac, a simple and versatile system for generating recombinant baculovirus DNA to express protein complexes compr...
journal_title：Nature biotechnology
pub_type： 信件
doi：10.1038/nbt1036
更新日期：2004-12-01 00:00:00
abstract：:The potential therapeutic applications of encapsulated cells are enormous. In the US alone, it has been estimated that nearly half-a-trillion dollars are spent each year to care for patients who suffer tissue loss or dysfunction. Over 6 million patients suffer from neurodegenerative disorders such as Alzheimer's disea...
journal_title：Nature biotechnology
pub_type： 杂志文章,评审
doi：10.1038/nbt0996-1107
更新日期：1996-09-01 00:00:00
abstract：:The Human Proteome Organization (HUPO) recently completed the first large-scale collaborative study to characterize the human serum and plasma proteomes. The study was carried out in different locations and used diverse methods and instruments to compare and integrate tandem mass spectrometry (MS/MS) data on aliquots ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt1183
更新日期：2006-03-01 00:00:00
abstract：:We constructed an immunotoxin, composed of an antibody directed against the high-affinity IgG receptor CD64 and Ricin-A, with the aim of resolving chronic inflammation through elimination of activated macrophages. In vitro, this immunotoxin proved very efficient in inducing apoptosis in activated macrophages, leaving ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/71908
更新日期：2000-01-01 00:00:00
abstract：:Epigenetic modifications constitute a complex regulatory layer on top of the genome sequence. Pluripotent and differentiated cells provide a powerful system for investigating how the epigenetic code influences cellular fate. High-throughput sequencing of these cell types has yielded DNA methylation maps at single-nucl...
journal_title：Nature biotechnology
pub_type： 杂志文章,评审
doi：10.1038/nbt.1684
更新日期：2010-10-01 00:00:00
abstract：:A T-cell receptor mimic peptide (TCRpep) consisting of an 8-amino-acid peptide, homologous to the transmembrane region of the T-cell receptor (TCR) alpha chain, blocks T-cell activation after systemic application. When dendritic cells (DCs) were transduced to secrete the TCRpep and injected into mice, evidence of immu...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt842
更新日期：2003-08-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature biotechnology
pub_type： 已发布勘误
doi：10.1038/s41587-019-0253-5
更新日期：2019-09-01 00:00:00
abstract：:The specificity of biological regulatory mechanisms relies on selective interactions between different proteins in different cell types and in response to different extracellular signals. We describe a bimolecular fluorescence complementation (BiFC) approach for the simultaneous visualization of multiple protein inter...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt816
更新日期：2003-05-01 00:00:00
abstract：:RNA-guided genome editing with the CRISPR-Cas9 system has great potential for basic and clinical research, but the determinants of targeting specificity and the extent of off-target cleavage remain insufficiently understood. Using chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we mapped genom...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.2916
更新日期：2014-07-01 00:00:00
abstract：:Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6%∼96.7%...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3208
更新日期：2015-05-01 00:00:00
abstract：:Influenza A virus leads to yearly epidemics and sporadic pandemics. Present prophylactic strategies focus on egg-grown, live, attenuated influenza vaccines (LAIVs), in which attenuation is generated by conferring temperature sensitivity onto the virus. Here we describe an alternative approach to attenuating influenza ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.1542
更新日期：2009-06-01 00:00:00
abstract：:Fewer than half of all tandem mass spectrometry (MS/MS) spectra acquired in shotgun proteomics experiments are typically matched to a peptide with high confidence. Here we determine the identity of unassigned peptides using an ultra-tolerant Sequest database search that allows peptide matching even with modifications ...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3267
更新日期：2015-07-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature biotechnology
pub_type： 已发布勘误
doi：10.1038/s41587-019-0292-y
更新日期：2019-11-01 00:00:00
abstract：:Most microorganisms from all taxonomic levels are uncultured. Single-cell genomes and metagenomes continue to increase the known diversity of Bacteria and Archaea; however, while 'omics can be used to infer physiological or ecological roles for species in a community, most of these hypothetical roles remain unvalidate...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/s41587-019-0260-6
更新日期：2019-11-01 00:00:00
abstract：:Industrial strain development requires system-wide engineering and optimization of cellular metabolism while considering industrially relevant fermentation and recovery processes. It can be conceptualized as several strategies, which may be implemented in an iterative fashion and in different orders. The key challenge...
journal_title：Nature biotechnology
pub_type： 杂志文章,评审
doi：10.1038/nbt.3365
更新日期：2015-10-01 00:00:00
abstract：:In the version of this article initially published, a GlaxoSmithKline compound referred to as GSK298559 was listed in Table 1 as a RIPK1 inhibitor in phase 1 trials for inflammatory bowel disease. The correct designation is GSK2983559; however, this compound is a RIPK2 inhibitor and thus should not have been included ...
journal_title：Nature biotechnology
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41587-019-0082-6
更新日期：2019-04-01 00:00:00
abstract：:Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AA...
journal_title：Nature biotechnology
pub_type： 杂志文章
doi：10.1038/nbt.3440
更新日期：2016-02-01 00:00:00
