当前位置： SCI文献检索 > NATURE BIOTECHNOLOGY期刊下所有文献 > Increasing the size of rAAV-mediated expression cassettes in vivo by intermolecular joining of two complementary vectors.

Increasing the size of rAAV-mediated expression cassettes in vivo by intermolecular joining of two complementary vectors.

Abstract：

:A major shortcoming to the use of adeno-associated virus (rAAV) vectors is their limited packaging size. To overcome this hurdle, we split an expression cassette and cloned it into two separate vectors. The vectors contained either a nuclear localizing Escherichia coli lacZ transgene (nlslacZ) with a splice acceptor, or the human elongation factor 1alpha ( EF1alpha) gene enhancer/promoter(s) (EF1alphaEP) with a splice donor. We co-injected a promoter-less nlslacZ vector with a vector containing either a single EF1alphaEP or a double copy of the EF1alphaEP in a head-to-head orientation, into the portal vein of mice. Gene expression, measured by both transduction efficiency and quantitation of the recombinant protein, was as much as 60-70% of that obtained from mice that received a single vector containing a complete EFalphaEP/nlslacZ expression cassette. This two-vector approach may allow development of gene therapy strategies that will carry exogenous DNA sequences with large therapeutic cDNAs and/or regulatory elements.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Nakai H,Storm TA,Kay MA

doi

10.1038/75390

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

527-32

issue

5

eissn

1087-0156

issn

1546-1696

journal_volume

18

pub_type

杂志文章

相关文献

NATURE BIOTECHNOLOGY文献大全
  • Inovio.

    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

    authors： Rohn J

    更新日期：2013-02-01 00:00:00

  • Microbial synthesis of medium-chain chemicals from renewables.

    abstract：:Linear, medium-chain (C8-C12) hydrocarbons are important components of fuels as well as commodity and specialty chemicals. As industrial microbes do not contain pathways to produce medium-chain chemicals, approaches such as overexpression of endogenous enzymes or deletion of competing pathways are not available to the...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,评审

    doi：10.1038/nbt.4022

    authors： Sarria S,Kruyer NS,Peralta-Yahya P

    更新日期：2017-12-01 00:00:00

  • Directed evolution of proteins by exon shuffling.

    abstract：:Evolution of eukaryotes is mediated by sexual recombination of parental genomes. Crossovers occur in random, but homologous, positions at a frequency that depends on DNA length. As exons occupy only 1% of the human genome and introns about 24%, by far most of the crossovers occur between exons, rather than inside. The...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,评审

    doi：10.1038/88084

    authors： Kolkman JA,Stemmer WP

    更新日期：2001-05-01 00:00:00

  • Author Correction: A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae.

    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/s41587-020-0658-1

    authors： Simoni A,Hammond AM,Beaghton AK,Galizi R,Taxiarchi C,Kyrou K,Meacci D,Gribble M,Morselli G,Burt A,Nolan T,Crisanti A

    更新日期：2020-09-01 00:00:00

  • Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown.

    abstract：:A central hurdle in developing small interfering RNAs (siRNAs) as therapeutics is the inefficiency of their delivery across the plasma and endosomal membranes to the cytosol, where they interact with the RNA interference machinery. With the aim of improving endosomal release, a poorly understood and inefficient proces...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.3298

    authors： Wittrup A,Ai A,Liu X,Hamar P,Trifonova R,Charisse K,Manoharan M,Kirchhausen T,Lieberman J

    更新日期：2015-08-01 00:00:00

  • Synthetic CD4 exocyclics inhibit binding of human immunodeficiency virus type 1 envelope to CD4 and virus replication in T lymphocytes.

    abstract：:CD4 functions as a major T-cell surface receptor for human immunodeficiency virus by binding the human immunodeficiency virus type 1 (HIV-1) envelope protein gp120 with relatively high affinity. We have developed constrained aromatically modified analogs of the secondary structures of the first domain of CD4 in order ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0297-150

    authors： Zhang X,Gaubin M,Briant L,Srikantan V,Murali R,Saragovi U,Weiner D,Devaux C,Autiero M,Piatier-Tonneau D,Greene MI

    更新日期：1997-02-01 00:00:00

  • Efficient siRNA delivery into primary cells by a peptide transduction domain-dsRNA binding domain fusion protein.

    abstract：:RNA interference (RNAi) induced by short interfering RNA (siRNA) allows for discovery research and large-scale screening; however, owing to their size and anionic charge, siRNAs do not readily enter cells. Current approaches do not deliver siRNAs into a high percentage of primary cells without cytotoxicity. Here we re...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.1541

    authors： Eguchi A,Meade BR,Chang YC,Fredrickson CT,Willert K,Puri N,Dowdy SF

    更新日期：2009-06-01 00:00:00

  • Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo.

    abstract：:Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implant...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt1393

    authors： Kroon E,Martinson LA,Kadoya K,Bang AG,Kelly OG,Eliazer S,Young H,Richardson M,Smart NG,Cunningham J,Agulnick AD,D'Amour KA,Carpenter MK,Baetge EE

    更新日期：2008-04-01 00:00:00

  • Full-length transcriptome assembly from RNA-Seq data without a reference genome.

    abstract：:Massively parallel sequencing of cDNA has enabled deep and efficient probing of transcriptomes. Current approaches for transcript reconstruction from such data often rely on aligning reads to a reference genome, and are thus unsuitable for samples with a partial or missing reference genome. Here we present the Trinity...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.1883

    authors： Grabherr MG,Haas BJ,Yassour M,Levin JZ,Thompson DA,Amit I,Adiconis X,Fan L,Raychowdhury R,Zeng Q,Chen Z,Mauceli E,Hacohen N,Gnirke A,Rhind N,di Palma F,Birren BW,Nusbaum C,Lindblad-Toh K,Friedman N,Regev A

    更新日期：2011-05-15 00:00:00

  • Construction of YAC-based mammalian artificial chromosomes.

    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

    authors： Ikeno M,Grimes B,Okazaki T,Nakano M,Saitoh K,Hoshino H,McGill NI,Cooke H,Masumoto H

    更新日期：1998-05-01 00:00:00

  • Flexibility--the guiding principle for antibody manufacturing.

    abstract：:Ensuring adequate manufacturing capacity for recombinant and monoclonal antibodies is one of the greatest challenges facing the biotech industry. The following factors should be taken into account when designing product development and production strategies. ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0905-1054

    authors： Carson KL

    更新日期：2005-09-01 00:00:00

  • Engineered off-the-shelf therapeutic T cells resist host immune rejection.

    abstract：:Engineered T cells are effective therapies against a range of malignancies, but current approaches rely on autologous T cells, which are difficult and expensive to manufacture. Efforts to develop potent allogeneic T cells that are not rejected by the recipient's immune system require abrogating both T- and natural kil...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/s41587-020-0601-5

    authors： Mo F,Watanabe N,McKenna MK,Hicks MJ,Srinivasan M,Gomes-Silva D,Atilla E,Smith T,Ataca Atilla P,Ma R,Quach D,Heslop HE,Brenner MK,Mamonkin M

    更新日期：2021-01-01 00:00:00

  • Phosphoramidate oligonucleotides as potent antisense molecules in cells and in vivo.

    abstract：:Antisense oligonucleotides are designed to specifically hybridize to a target messenger RNA (mRNA) and interfere with the synthesis of the encoded protein. Uniformly modified oligonucleotides containing N3'-P5' phosphoramidate linkages exhibit (NP) extremely high-affinity binding to single-stranded RNA, do not induce ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/83489

    authors： Faria M,Spiller DG,Dubertret C,Nelson JS,White MR,Scherman D,Hélène C,Giovannangeli C

    更新日期：2001-01-01 00:00:00

  • Engineering soluble proteins for structural genomics.

    abstract：:Structural genomics has the ambitious goal of delivering three-dimensional structural information on a genome-wide scale. Yet only a small fraction of natural proteins are suitable for structure determination because of bottlenecks such as poor expression, aggregation, and misfolding of proteins, and difficulties in s...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt732

    authors： Pédelacq JD,Piltch E,Liong EC,Berendzen J,Kim CY,Rho BS,Park MS,Terwilliger TC,Waldo GS

    更新日期：2002-09-01 00:00:00

  • Continuous evolution of SpCas9 variants compatible with non-G PAMs.

    abstract：:The targeting scope of Streptococcus pyogenes Cas9 (SpCas9) and its engineered variants is largely restricted to protospacer-adjacent motif (PAM) sequences containing G bases. Here we report the evolution of three new SpCas9 variants that collectively recognize NRNH PAMs (where R is A or G and H is A, C or T) using ph...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/s41587-020-0412-8

    authors： Miller SM,Wang T,Randolph PB,Arbab M,Shen MW,Huang TP,Matuszek Z,Newby GA,Rees HA,Liu DR

    更新日期：2020-04-01 00:00:00

  • Automated assembly of centromeres from ultra-long error-prone reads.

    abstract：:Centromeric variation has been linked to cancer and infertility, but centromere sequences contain multiple tandem repeats and can only be assembled manually from long error-prone reads. Here we describe the centroFlye algorithm for centromere assembly using long error-prone reads, and apply it to assemble human centro...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/s41587-020-0582-4

    authors： Bzikadze AV,Pevzner PA

    更新日期：2020-11-01 00:00:00

  • A dual-constriction biological nanopore resolves homonucleotide sequences with high fidelity.

    abstract：:Single-molecule long-read DNA sequencing with biological nanopores is fast and high-throughput but suffers reduced accuracy in homonucleotide stretches. We now combine the CsgG nanopore with the 35-residue N-terminal region of its extracellular interaction partner CsgF to produce a dual-constriction pore with improved...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/s41587-020-0570-8

    authors： Van der Verren SE,Van Gerven N,Jonckheere W,Hambley R,Singh P,Kilgour J,Jordan M,Wallace EJ,Jayasinghe L,Remaut H

    更新日期：2020-12-01 00:00:00

  • De novo reconstitution of a functional mammalian urinary bladder by tissue engineering.

    abstract：:Human organ replacement is limited by a donor shortage, problems with tissue compatibility, and rejection. Creation of an organ with autologous tissue would be advantageous. In this study, transplantable urinary bladder neo-organs were reproducibly created in vitro from urothelial and smooth muscle cells grown in cult...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/6146

    authors： Oberpenning F,Meng J,Yoo JJ,Atala A

    更新日期：1999-02-01 00:00:00

  • Prevention of systemic lupus erythematosus in MRL/lpr mice by administration of an immunoglobulin-binding peptide.

    abstract：:Systemic lupus erythematosus (SLE) is a multisystem chronic inflammatory disease of unknown etiology that affects many organs, including the kidney. The presence of multiple autoantibodies and other immunological abnormalities point to basic defects in immunoregulatory controls that normally maintain self-tolerance. T...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/77296

    authors： Marino M,Ruvo M,De Falco S,Fassina G

    更新日期：2000-07-01 00:00:00

  • The search for the ideal biocatalyst.

    abstract：:While the use of enzymes as biocatalysts to assist in the industrial manufacture of fine chemicals and pharmaceuticals has enormous potential, application is frequently limited by evolution-led catalyst traits. The advent of designer biocatalysts, produced by informed selection and mutation through recombinant DNA tec...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,评审

    doi：10.1038/nbt0102-37

    authors： Burton SG,Cowan DA,Woodley JM

    更新日期：2002-01-01 00:00:00

  • Resolution of cutaneous inflammation after local elimination of macrophages.

    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

    authors： Thepen T,van Vuuren AJ,Kiekens RC,Damen CA,Vooijs WC,van De Winkel JG

    更新日期：2000-01-01 00:00:00

  • Programmable m6A modification of cellular RNAs with a Cas13-directed methyltransferase.

    abstract：:N6-Methyladenosine (m6A) is the most widespread internal messenger RNA modification in humans. Despite recent progress in understanding the biological roles of m6A, the inability to install m6A site specifically in individual transcripts has hampered efforts to elucidate causal relationships between the presence of a ...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/s41587-020-0572-6

    authors： Wilson C,Chen PJ,Miao Z,Liu DR

    更新日期：2020-12-01 00:00:00

  • Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes.

    abstract：:Isoflavones have drawn much attention because of their benefits to human health. These compounds, which are produced almost exclusively in legumes, have natural roles in plant defense and root nodulation. Isoflavone synthase catalyzes the first committed step of isoflavone biosynthesis, a branch of the phenylpropanoid...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/72671

    authors： Jung W,Yu O,Lau SM,O'Keefe DP,Odell J,Fader G,McGonigle B

    更新日期：2000-02-01 00:00:00

  • Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome.

    abstract：:Escherichia coli-based artificial chromosomes have become important tools for physical mapping and sequencing in various genome projects. The lack of a general method to modify these large bacterial clones, however, has limited their utility in functional studies. We developed a simple method to modify bacterial artif...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt0997-859

    authors： Yang XW,Model P,Heintz N

    更新日期：1997-09-01 00:00:00

  • Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells.

    abstract：:Of paramount importance for the development of cell therapies to treat diabetes is the production of sufficient numbers of pancreatic endocrine cells that function similarly to primary islets. We have developed a differentiation process that converts human embryonic stem (hES) cells to endocrine cells capable of synth...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt1259

    authors： D'Amour KA,Bang AG,Eliazer S,Kelly OG,Agulnick AD,Smart NG,Moorman MA,Kroon E,Carpenter MK,Baetge EE

    更新日期：2006-11-01 00:00:00

  • Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates.

    abstract：:The reactive thiol in cysteine is used for coupling maleimide linkers in the generation of antibody conjugates. To assess the impact of the conjugation site, we engineered cysteines into a therapeutic HER2/neu antibody at three sites differing in solvent accessibility and local charge. The highly solvent-accessible si...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt.2108

    authors： Shen BQ,Xu K,Liu L,Raab H,Bhakta S,Kenrick M,Parsons-Reponte KL,Tien J,Yu SF,Mai E,Li D,Tibbitts J,Baudys J,Saad OM,Scales SJ,McDonald PJ,Hass PE,Eigenbrot C,Nguyen T,Solis WA,Fuji RN,Flagella KM,Patel D,Spe

    更新日期：2012-01-22 00:00:00

  • Data storage in DNA with fewer synthesis cycles using composite DNA letters.

    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

    authors： Anavy L,Vaknin I,Atar O,Amit R,Yakhini Z

    更新日期：2019-10-01 00:00:00

  • The chemical evolution of oligonucleotide therapies of clinical utility.

    abstract：:After nearly 40 years of development, oligonucleotide therapeutics are nearing meaningful clinical productivity. One of the key advantages of oligonucleotide drugs is that their delivery and potency are derived primarily from the chemical structure of the oligonucleotide whereas their target is defined by the base seq...

    journal_title：Nature biotechnology

    pub_type： 杂志文章,评审

    doi：10.1038/nbt.3765

    authors： Khvorova A,Watts JK

    更新日期：2017-03-01 00:00:00

  • Applications of CRISPR technologies in research and beyond.

    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

    authors： Barrangou R,Doudna JA

    更新日期：2016-01-01 00:00:00

  • Redirecting lipoic acid ligase for cell surface protein labeling with small-molecule probes.

    abstract：:Live cell imaging is a powerful method to study protein dynamics at the cell surface, but conventional imaging probes are bulky, or interfere with protein function, or dissociate from proteins after internalization. Here, we report technology for covalent, specific tagging of cellular proteins with chemical probes. Th...

    journal_title：Nature biotechnology

    pub_type： 杂志文章

    doi：10.1038/nbt1355

    authors： Fernández-Suárez M,Baruah H,Martínez-Hernández L,Xie KT,Baskin JM,Bertozzi CR,Ting AY

    更新日期：2007-12-01 00:00:00