Abstract:
:A major obstacle to stem-cell gene therapy rests in the inability to deliver a gene into a therapeutically relevant fraction of stem cells. One way to circumvent this obstacle is to use selection. Vectors containing two linked genes serve as the basis for selection, with one gene encoding a selectable product and the other, a therapeutic protein. Applying selection in vivo has the potential to bring a minor population of genetically corrected cells into the therapeutic range. But strategies for achieving in vivo selection have traditionally relied on genes that confer resistance to cytotoxic drugs and are encumbered by toxicity. Here we describe a new system for in vivo selection that uses a 'cell-growth switch', allowing a minor population of genetically corrected cells into the therapeutic range. But strategies for achieving in vivo selection have traditionally relied on genes that confer resistance to cytotoxic drugs and are encumbered by toxicity. Here we describe a new system for in vivo selection that uses a 'cell-growth switch', allowing a minor population of genetically modified cells to be inducibly amplified, thereby averting the risks associated with cytotoxic drugs. This system provides a general platform for conditionally expanding genetically modified cell populations in vivo, and may have widespread applications in gene and cell therapy.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Jin L,Zeng H,Chien S,Otto KG,Richard RE,Emery DW,Blau CAdoi
10.1038/79194keywords:
subject
Has Abstractpub_date
2000-09-01 00:00:00pages
64-6issue
1eissn
1061-4036issn
1546-1718journal_volume
26pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::Familial hypomagnesemia with secondary hypocalcemia (OMIM 602014) is an autosomal recessive disease that results in electrolyte abnormalities shortly after birth. Affected individuals show severe hypomagnesemia and hypocalcemia, which lead to seizures and tetany. The disorder has been thought to be caused by a defect ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng901
更新日期:2002-06-01 00:00:00
abstract::The Human Genome Project and its spin-offs are making it increasingly feasible to determine the genetic basis of complex traits using genome-wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1582
更新日期:2005-07-01 00:00:00
abstract::Copy number variations (CNVs) often include noncoding sequences and putative enhancers, but how these rearrangements induce disease is poorly understood. Here we investigate CNVs involving the regulatory landscape of IHH (encoding Indian hedgehog), which cause multiple, highly localized phenotypes including craniosyno...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3939
更新日期:2017-10-01 00:00:00
abstract::Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS an...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng2099
更新日期:2007-08-01 00:00:00
abstract::Junctional epidermolysis bullosa (JEB) is a heterogeneous autosomal recessively inherited blistering skin disorder associated with fragility at the dermal-epidermal junction. Characteristic ultrastructural findings in JEB are abnormalities in the hemidesmosome-anchoring filament complexes. These focal attachment struc...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0995-83
更新日期:1995-09-01 00:00:00
abstract::An ever-larger proportion of the liability to common and complex disease can be obtained by progressively larger studies. However, for most diseases, the sample sizes required to gain usable predictions will be out of reach of sequencing technologies for the foreseeable future. Array-based genotyping genome-wide assoc...
journal_title:Nature genetics
pub_type: 社论
doi:10.1038/ng.2605
更新日期:2013-04-01 00:00:00
abstract::Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemo...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.466
更新日期:2009-11-01 00:00:00
abstract::In the version of this article initially published, affiliation 38 incorrectly read "ICNU-Nephrology and Urology Department, Barcelona, Spain"; "Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain" is the correct affiliation. The error has been corrected in the HTML and PDF versions of ...
journal_title:Nature genetics
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41588-019-0376-0
更新日期:2019-04-01 00:00:00
abstract::Micro RNAs are a large family of noncoding RNAs of 21-22 nucleotides whose functions are generally unknown. Here a large subset of Drosophila micro RNAs is shown to be perfectly complementary to several classes of sequence motif previously demonstrated to mediate negative post-transcriptional regulation. These finding...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng865
更新日期:2002-04-01 00:00:00
abstract::To ascertain the role of cyclin-dependent kinase 4 (Cdk4) in vivo, we have targeted the mouse Cdk4 locus by homologous recombination to generate two strains of mice, one that lacks Cdk4 expression and one that expresses a Cdk4 molecule with an activating mutation. Embryonic fibroblasts proliferate normally in the abse...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/8751
更新日期:1999-05-01 00:00:00
abstract::Plants intimately associate with diverse bacteria. Plant-associated bacteria have ostensibly evolved genes that enable them to adapt to plant environments. However, the identities of such genes are mostly unknown, and their functions are poorly characterized. We sequenced 484 genomes of bacterial isolates from roots o...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-017-0012-9
更新日期:2017-12-18 00:00:00
abstract::The Syrian cardiomyopathic hamster (BIO14.6) has an inherited form of progressive myocardial necrosis and congestive heart failure. Although widely studied as an animal model for human hypertrophic cardiomyopathy, further genetic analysis has been limited by a scarcity of DNA markers. Until now, only six autosomal lin...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0596-87
更新日期:1996-05-01 00:00:00
abstract::The histone variant H3.3 is enriched at enhancers and active genes, as well as repeat regions such as telomeres and retroelements, in mouse embryonic stem cells (mESCs)1-3. Although recent studies demonstrate a role for H3.3 and its chaperones in establishing heterochromatin at repeat regions4-8, the function of H3.3 ...
journal_title:Nature genetics
pub_type: 信件
doi:10.1038/s41588-019-0428-5
更新日期:2019-06-01 00:00:00
abstract::The most characteristic features of bipolar affective disorder (manic-depressive illness) are episodes of mania (bipolar I, BPI) or hypomania (bipolar II, BPII) interspersed with periods of depression. Manic-depressive illness afflicts about one percent of the population, and if untreated, is associated with an approx...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0496-431
更新日期:1996-04-01 00:00:00
abstract::By imposing a limit on the proliferative lifespan of most somatic cells, telomere erosion represents an innate mechanism for tumor suppression and may contribute to age-related disease. A detailed understanding of the pathways that link shortened telomeres to replicative senescence has been severely hindered by the in...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1084
更新日期:2003-02-01 00:00:00
abstract::Cretinism is marked by irreversible mental and growth retardation. We describe here an entirely new case of cretinism showing combined pituitary hormone deficiencies of thyrotropin, growth hormone and prolactin that appears to be caused by homozygosity for a nonsense mutation in the gene for the pituitary specific tra...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0492-56
更新日期:1992-04-01 00:00:00
abstract::We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atheroscleros...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1245
更新日期:2003-10-01 00:00:00
abstract::Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide ass...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3340
更新日期:2015-08-01 00:00:00
abstract::Transcription of the 2.5 megabase dystrophin gene gives rise to multiple isoforms. We describe a 5.2 kilobase transcript, expressed specifically in peripheral nerve, that initiates at a previously unrecognized exon located approximately 850 basepairs upstream of dystrophin exon 56. The likely product of this transcrip...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0593-77
更新日期:1993-05-01 00:00:00
abstract::Variation for metabolite composition and content is often observed in plants. However, it is poorly understood to what extent this variation has a genetic basis. Here, we describe the genetic analysis of natural variation in the metabolite composition in Arabidopsis thaliana. Instead of focusing on specific metabolite...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1815
更新日期:2006-07-01 00:00:00
abstract:: ...
journal_title:Nature genetics
pub_type: 评论,杂志文章
doi:10.1038/s41588-018-0317-3
更新日期:2019-01-01 00:00:00
abstract::In the HTML version of this article initially published, the name of author Diletta Di Mitri was miscoded in the XML such that Di was included as part of the given name instead of the family name. The error has been corrected in the HTML version of the article. ...
journal_title:Nature genetics
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41588-018-0181-1
更新日期:2018-09-01 00:00:00
abstract::Volumetric variations of the human brain are heritable and are associated with many brain-related complex traits. Here we performed genome-wide association studies (GWAS) of 101 brain volumetric phenotypes using the UK Biobank sample including 19,629 participants. GWAS identified 365 independent genetic variants excee...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-019-0516-6
更新日期:2019-11-01 00:00:00
abstract::Cell division is controlled by a series of positive and negative regulators which act at sequential points throughout the cell cycle. Disturbance of these checks could contribute to cancer by allowing excessive cell proliferation. The point in G1 at which cells irrevocably commit to DNA synthesis is controlled by prot...
journal_title:Nature genetics
pub_type: 信件
doi:10.1038/ng0595-114
更新日期:1995-05-01 00:00:00
abstract::Human telomeres are composed of long arrays of TTAGGG repeats that form a nucleoprotein complex required for the protection and replication of chromosome ends. One component of human telomeres is the TTAGGG repeat binding factor 1 (TRF1), a ubiquitously expressed protein, related to the protooncogene Myb, that is pres...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1097-231
更新日期:1997-10-01 00:00:00
abstract::Animal development is an extremely robust process resulting in stereotyped outcomes. Canalization is a design principle wherein developmental pathways are stabilized to increase phenotypic reproducibility. Recent revelations into microRNA (miRNA) function suggest that miRNAs act as key players in canalizing genetic pr...
journal_title:Nature genetics
pub_type: 杂志文章,评审
doi:10.1038/ng1803
更新日期:2006-06-01 00:00:00
abstract::Partial exclusion mapping of the nonobese (NOD) diabetic mouse genome has shown linkage of diabetes to at least five different chromosomes. We have now excluded almost all of the genome for the presence of susceptibility genes with fully recessive effects and have obtained evidence of linkage of ten distinct loci to d...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0893-404
更新日期:1993-08-01 00:00:00
abstract::The abundance of transposable elements and DNA repeat sequences in mammalian genomes raises the question of whether such insertions represent passive evolutionary baggage or may influence the expression of complex traits. We addressed this question in Drosophila melanogaster, in which the effects of single transposabl...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1823
更新日期:2006-07-01 00:00:00
abstract::Wilson disease (WD) is an autosomal recessive disorder of copper transport which map to chromosome 13q14.3. In pursuit of the WD gene, we developed yeast artificial chromosome and cosmid contigs, and microsatellite markers which span the WD gene region. Linkage disequilibrium and haplotype analysis of 115 WD families ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1293-338
更新日期:1993-12-01 00:00:00
abstract::Gene-environment associations are important in rheumatoid arthritis (RA) susceptibility, with an association existing between smoking, HLA- DRB1 'shared epitope' alleles, PTPN22 and antibodies to cyclic citrullinated peptides (CCP). Here, we test the hypothesis that a subset of the anti-CCP response, with specific aut...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.480
更新日期:2009-12-01 00:00:00