Abstract:
:We used the integrase from phage phiC31 to integrate the human Factor IX (hFIX) gene permanently into specific sites in the mouse genome. A plasmid containing attB and an expression cassette for hFIX was delivered to the livers of mice by using high-pressure tail vein injection. When an integrase expression plasmid was co-injected, hFIX serum levels increased more than tenfold to approximately 4 microg/ml, similar to normal FIX levels, and remained stable throughout the more than eight months of the experiment. hFIX levels persisted after partial hepatectomy, suggesting genomic integration of the vector. Site-specific integration was proven by characterizing and quantifying genomic integration in the liver at the DNA level. Integration was documented at two pseudo-attP sites, native sequences with partial identity to attP, with one site highly predominant. This study demonstrates in vivo gene transfer in an animal by site-specific genomic integration.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Olivares EC,Hollis RP,Chalberg TW,Meuse L,Kay MA,Calos MPdoi
10.1038/nbt753subject
Has Abstractpub_date
2002-11-01 00:00:00pages
1124-8issue
11eissn
1087-0156issn
1546-1696pii
nbt753journal_volume
20pub_type
杂志文章abstract::In vitro reprogramming of somatic cells into a pluripotent embryonic stem cell-like state has been achieved through retroviral transduction of murine fibroblasts with Oct4, Sox2, c-myc and Klf4. In these experiments, the rare 'induced pluripotent stem' (iPS) cells were isolated by stringent selection for activation of...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1335
更新日期:2007-10-01 00:00:00
abstract::The re-use of previously validated designs is critical to the evolution of synthetic biology from a research discipline to an engineering practice. Here we describe the Synthetic Biology Open Language (SBOL), a proposed data standard for exchanging designs within the synthetic biology community. SBOL represents synthe...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2891
更新日期:2014-06-01 00:00:00
abstract::We introduce Sailfish, a computational method for quantifying the abundance of previously annotated RNA isoforms from RNA-seq data. Because Sailfish entirely avoids mapping reads, a time-consuming step in all current methods, it provides quantification estimates much faster than do existing approaches (typically 20 ti...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2862
更新日期:2014-05-01 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::Foxtail millet (Setaria italica), a member of the Poaceae grass family, is an important food and fodder crop in arid regions and has potential for use as a C(4) biofuel. It is a model system for other biofuel grasses, including switchgrass and pearl millet. We produced a draft genome (∼423 Mb) anchored onto nine chrom...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2195
更新日期:2012-05-13 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::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::The biology of multicellular organisms is coordinated across multiple size scales, from the subnanoscale of molecules to the macroscale, tissue-wide interconnectivity of cell populations. Here we introduce a method for super-resolution imaging of the multiscale organization of intact tissues. The method, called magnif...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3641
更新日期:2016-09-01 00:00:00
abstract::Delivery of short interfering RNAs (siRNAs) remains a key challenge in the development of RNA interference (RNAi) therapeutics. A better understanding of the mechanisms of siRNA cellular uptake, intracellular transport and endosomal release could critically contribute to the improvement of delivery methods. Here we mo...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2612
更新日期:2013-07-01 00:00:00
abstract::To construct a mammalian artificial chromosome (MAC), telomere repeats and selectable markers were introduced into a 100 kb yeast artificial chromosome (YAC) containing human centromeric DNA. This YAC, which has a regular repeat structure of alpha-satellite DNA and centromere protein B (CENP-B) boxes, efficiently form...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt0598-431
更新日期:1998-05-01 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::The density and long-term stability of DNA make it an appealing storage medium, particularly for long-term data archiving. Existing DNA storage technologies involve the synthesis and sequencing of multiple nominally identical molecules in parallel, resulting in information redundancy. We report the development of enco...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0240-x
更新日期:2019-10-01 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::We describe tethered conformation capture (TCC), a method for genome-wide mapping of chromatin interactions. By performing ligations on solid substrates rather than in solution, TCC substantially enhances the signal-to-noise ratio, thereby facilitating a detailed analysis of interactions within and between chromosomes...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2057
更新日期:2011-12-25 00:00:00
abstract::RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA. RNAi holds great promise as a novel nucleic acid-based therapeutic against a wide variety of diseases, including cancer, infectious diseases and genetic disorders. Antiviral RNAi strategies have r...
journal_title:Nature biotechnology
pub_type: 杂志文章,评审
doi:10.1038/nbt1369
更新日期:2007-12-01 00:00:00
abstract::Programmable DNA cleavage using CRISPR-Cas9 enables efficient, site-specific genome engineering in single cells and whole organisms. In the research arena, versatile CRISPR-enabled genome editing has been used in various ways, such as controlling transcription, modifying epigenomes, conducting genome-wide screens and ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.3659
更新日期:2016-01-01 00:00:00
abstract::The clinical translation of cationic α-helical antimicrobial peptides (AMPs) has been hindered by structural instability, proteolytic degradation and in vivo toxicity from nonspecific membrane lysis. Although analyses of hydrophobic content and charge distribution have informed the design of synthetic AMPs with increa...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-019-0222-z
更新日期:2019-10-01 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::Despite recent accomplishments, significant challenges remain before cloning can become a routine part of transgenic animal production. ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/80231
更新日期:2000-10-01 00:00:00
abstract::The scale and capabilities of single-cell RNA-sequencing methods have expanded rapidly in recent years, enabling major discoveries and large-scale cell mapping efforts. However, these methods have not been systematically and comprehensively benchmarked. Here, we directly compare seven methods for single-cell and/or si...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/s41587-020-0465-8
更新日期:2020-06-01 00:00:00
abstract::In the human malaria vector Anopheles gambiae, the gene doublesex (Agdsx) encodes two alternatively spliced transcripts, dsx-female (AgdsxF) and dsx-male (AgdsxM), that control differentiation of the two sexes. The female transcript, unlike the male, contains an exon (exon 5) whose sequence is highly conserved in all ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.4245
更新日期:2018-12-01 00:00:00
abstract::Field tests of corn co-expressing two new delta-endotoxins from Bacillus thuringiensis (Bt) have demonstrated protection from root damage by western corn rootworm (Diabrotica virgifera virgifera LeConte). The level of protection exceeds that provided by chemical insecticides. In the bacterium, these proteins form crys...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/90282
更新日期:2001-07-01 00:00:00
abstract::New high-dimensional, single-cell technologies offer unprecedented resolution in the analysis of heterogeneous tissues. However, because these technologies can measure dozens of parameters simultaneously in individual cells, data interpretation can be challenging. Here we present viSNE, a tool that allows one to map h...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.2594
更新日期:2013-06-01 00:00:00
abstract::Organophosphorus hydrolase (OPH) was displayed and anchored onto the surface of Escherichia coli using an Lpp-OmpA fusion system. Production of the fusion proteins in membrane fractions was verified by immunoblotting with OmpA antisera. Inclusion of the organophosphorus hydrolase signal sequence was necessary for achi...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1097-984
更新日期:1997-10-01 00:00:00
abstract::This report describes the selection of highly efficient antibody catalysts by combining chemical selection from a synthetic library with directed in vitro protein evolution. Evolution started from a naive antibody library displayed on phage made from fully synthetic, antibody-encoding genes (the Human Combinatorial An...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt828
更新日期:2003-06-01 00:00:00
abstract::Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical pract...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt1298
更新日期:2007-04-01 00:00:00
abstract::Increasing the in vivo residence times of protein therapeutics could decrease their dosing frequencies. We show that genetic fusion of an unstructured recombinant polypeptide of 864 amino acids, called XTEN, to a peptide or protein provides an apparently generic approach to extend plasma half-life. Allometric scaling ...
journal_title:Nature biotechnology
pub_type: 杂志文章
doi:10.1038/nbt.1588
更新日期:2009-12-01 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::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::A Pennsylvania company hopes to turn synthetic DNA vaccines into rapid response agents against flu epidemics and cancer. ...
journal_title:Nature biotechnology
pub_type: 新闻
doi:10.1038/nbt0213-98
更新日期:2013-02-01 00:00:00