Abstract：
:Genome editing with engineered nucleases (zinc finger, TAL effector, or CRISPR/Cas9-based) enables `write' access to regulatory programs executed by primary human cells. A decade of its clinical development, along with a reduction of conventional gene therapy to medical and commercial practice, has made cell reprogramming via editing a viable clinical modality. Reviewed here are the first examples of this to enter the clinic: ex vivo edited T cells for infectious disease and cancer, and hematopoietic stem/progenitor cells for the hemoglobinopathies. Three ongoing developments will ensure that the range of edited and reprogrammed cells to enter the clinic, and the scope of target indications, will grow markedly in the next five years: our ability to identify disease-relevant targets in noncoding regulatory DNA, which is uniquely suited for editing-based cell program control; recent reduction to clinical practice of in vivo editing; and progress in engineering and manufacture of differentiated cells from pluripotent progenitors.
journal_name
Curr Opin Genet Devjournal_title
Current opinion in genetics & developmentauthors
Urnov FDdoi
10.1016/j.gde.2018.05.005subject
Has Abstractpub_date
2018-10-01 00:00:00pages
48-56eissn
0959-437Xissn
1879-0380pii
S0959-437X(18)30061-3journal_volume
52pub_type
杂志文章,评审abstract：:SINEs with internal promoters for RNA polymerase III are ubiquitous in the genomes of the animal kingdom, including invertebrates. Although the human Alu family, and related families, originates from 7SL RNA, all other SINEs originate from tRNA. SINEs have been amplified many times, altered in genomic organization and...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(05)80198-4
更新日期：1991-12-01 00:00:00
abstract：:Over four decades ago, the first oscillations in metabolism in yeast cells were reported. Since then, multiple forms of oscillatory behavior have been observed in yeast grown under a variety of continuous culturing environments. The remarkable synchrony of cells undergoing such oscillations has made them ideal subject...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2010.09.008
更新日期：2010-12-01 00:00:00
abstract：:Molecules and cellular processes important for nervous system development can be repurposed in adulthood for the regulation of adult neurogenesis, synaptic plasticity, and neural regeneration following injury or degeneration. Efforts to recapitulate neural development in order to ameliorate injury or disease are promi...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2020.04.006
更新日期：2020-12-01 00:00:00
abstract：:The gene regulatory networks that control sex determination vary between species. Despite these differences, comparative studies in insects have found that alternative splicing is reiteratively used in evolution to control expression of the key sex-determining genes. Sex determination is best understood in Drosophila ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2011.03.001
更新日期：2011-08-01 00:00:00
abstract：:The Myc oncoprotein dimerizes with its partner, Max, to bind DNA, activate transcription, and promote cell proliferation, as well as programmed cell death. Max also forms homodimers or heterodimers with its alternative partners, Mad and Mxi-1. These complexes behave as antagonists of Myc/Max through competition for co...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(94)90098-1
更新日期：1994-02-01 00:00:00
abstract：:During the past year, significant advances have been made in understanding the functions of the oncoproteins, E6 and E7, of human papillomaviruses that are associated with malignant genital tumors. In addition, important new information is now available on the responses of both the keratinocyte and of the individual f...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(05)80329-6
更新日期：1992-02-01 00:00:00
abstract：:Proliferating cells must increase their mass coordinately with cell division. Recent evidence suggests that coupling of cell growth with cell division might be achieved by making synthesis of activators of cell division particularly sensitive to the capacity of the cell's protein synthesis machinery. ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(99)80011-2
更新日期：1999-02-01 00:00:00
abstract：:What determines phenotype is one of the most fundamental questions in biology. Historically, the search for answers had focused on genetic or environmental variants, but recent studies in epigenetics have revealed a third mechanism that can influence phenotypic outcomes, even in the absence of genetic or environmental...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2006.09.002
更新日期：2006-12-01 00:00:00
abstract：:In mammalian cells, four protein kinases form the PI3-kinase-related protein kinase (PIK) superfamily. These four enzymes-FRAP, DNA-PK, ATM, and ATR-are distinguished by their large size (all are >2500 amino acids), their common primary sequence relatedness through the carboxy-terminal protein kinase domain, and their...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(97)80125-6
更新日期：1997-04-01 00:00:00
abstract：:Acquired resistance is a major limitation for the successful treatment of cancer patients. Although numerous efficacious cancer therapeutics have been developed in the past decades, resistance arises due to a variety of reasons including tumoral genetic alterations, or modulation of factors in the tumor environment. U...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2019.02.006
更新日期：2019-02-01 00:00:00
abstract：:Radiotherapy is a form of cancer treatment that utilizes the ability of ionizing radiation to induce cell inactivation and cell death, generally via inflicting DNA double-strand breaks. However, different tumors and their normal surrounding tissues are not equally sensitive to radiation, posing a major challenge in th...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2013.01.002
更新日期：2013-02-01 00:00:00
abstract：:The relationships among in vivo chromatin structures, chromosome organization and genome function must be understood in order to reveal the hidden regulatory information in our genomes. Rather than being stable architectural features, it appears that chromatin and chromosome conformations at all levels are highly dyna...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2006.08.002
更新日期：2006-10-01 00:00:00
abstract：:The induction of apoptosis of virus-infected cells is an important host defense mechanism against invading pathogens. Some viruses express anti-apoptotic proteins that efficiently block apoptosis induced by death receptors or in response to stress signaled through mitochondria. Viral interference with host cell apopto...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(98)80066-x
更新日期：1998-02-01 00:00:00
abstract：:Understanding the past is to understand the present. Mammalian life, with all its complexity comes from a humble beginning of a single fertilized egg cell. Achieving this requires an enormous diversification of cellular function, the majority of which is generated through a series of cellular decisions during embryoge...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2015.08.002
更新日期：2015-10-01 00:00:00
abstract：:DNA sequence data are generally interpreted as favouring Kimura's neutral theory but not without dissent and often with a great deal of controversy with respect to molecular clocks, DNA polymorphism, adaptive evolution, and gene genealogy. Although the theory serves as a guiding principle, many issues concerning mutat...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(96)80034-7
更新日期：1996-12-01 00:00:00
abstract：:The establishment of left-right asymmetries in the vertebrate embryo is carried out by complex genetic interactions that impart left- or right-sided information to the developing organs and structures. The origin of LR information is still unclear, but recent advances have provided new insights as to how it is relayed...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2004.07.011
更新日期：2004-10-01 00:00:00
abstract：:The formation and anteroposterior patterning of the three definitive germ layers, ectoderm, or epiblast, is the common theme of vertebrate gastrulation. What changes from system to system is the geometry of these events and the nature of the non-epiblast transient structures implicated. A number of molecular markers, ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(95)80031-x
更新日期：1995-10-01 00:00:00
abstract：:The detection of sequence variation with restriction fragment length polymorphisms is advancing our knowledge of plant genetics on several fronts. In the past year, there has been progress in genetic map construction, phylogeny studies, and the dissection of multigenic traits. In addition, new methods that are indepen...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(91)80051-m
更新日期：1991-06-01 00:00:00
abstract：:Ras proteins activate a signaling cascade through direct binding of the serine/threonine kinase Raf. They also activate additional signaling pathways that are essential for full biological activity. Candidate effectors for these pathways include RalGDS and phosphatidyl inositol 3' kinase, as well as several other Ras ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(97)80112-8
更新日期：1997-02-01 00:00:00
abstract：:Unlike mammals, zebrafish are able to regenerate a damaged retina. Key to this regenerative response are Müller glia that respond to retinal injury by undergoing a reprogramming event that allows them to divide and generate a retinal progenitor that is multipotent and responsible for regenerating all major retinal neu...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2016.05.009
更新日期：2016-10-01 00:00:00
abstract：:The cloning of large DNAs as yeast artificial chromosomes (YACs) holds the promise of greatly expanding the scope of physical genomic mapping. Recent improvements in YAC clone libraries and their screening, as well as in the analysis of YAC-cloned DNA, are beginning to fulfill the potential of this system. ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(91)80044-m
更新日期：1991-06-01 00:00:00
abstract：:The mammalian globin gene clusters provide a paradigm for studying the relationship between genome structure and function. As blood stem cells undergo lineage specification and differentiation to form red blood cells, the chromatin structure and expression of the α-globin cluster change. The gradual activation of the ...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2020.10.003
更新日期：2020-11-19 00:00:00
abstract：:During development, embryos perform a mesmerizing choreography, which is crucial for the correct shaping, positioning and function of all organs. The cellular properties powering animal morphogenesis have been the focus of much attention. In contrast, much less consideration has been given to the invisible engine cons...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2019.06.015
更新日期：2019-08-01 00:00:00
abstract：:Family-based next generation sequencing (NGS) has recently pointed to an important role for de novo germline point mutations in both rare and common genetic disorders associated with reduced fitness. In this review we highlight the impact of the mutational target size on the frequency of diseases caused by these de no...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2013.01.007
更新日期：2013-06-01 00:00:00
abstract：:The advent of single-cell sequencing has been revolutionary to the field of cancer genomics. Perfectly suited to capture cancer's heterogeneous nature, single-cell analyses provide information bulk sequencing could never hope to uncover. Many mechanisms of cancer have yet to be fully understood, and single-cell approa...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2017.01.002
更新日期：2017-02-01 00:00:00
abstract：:Mutations in the BRCA1 and BRCA2 genes confer a high risk of breast cancer development. Both genes encode very large proteins of unknown function but recent results suggest that they may have roles in transcriptional regulation and DNA repair. These advances offer the prospect of understanding not only the normal cell...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/s0959-437x(98)80056-7
更新日期：1998-02-01 00:00:00
abstract：:Human genetic studies have long been vastly Eurocentric, raising a key question about the generalizability of these study findings to other populations. Because humans originated in Africa, these populations retain more genetic diversity, and yet individuals of African descent have been tremendously underrepresented i...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2018.08.005
更新日期：2018-12-01 00:00:00
abstract：:Recent studies on transposable elements (TEs) have shed light on the mechanisms that have shaped their evolution. In addition to accumulating nucleotide substitutions over evolutionary time, TEs appear to be especially prone to genetic rearrangements and vertical transmissions across even distantly related species. As...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/0959-437x(93)90005-a
更新日期：1993-12-01 00:00:00
abstract：:The discovery of induced pluripotent stem cells (iPSCs) has solidified the concept of transcription factors as major players in controlling cell identity and provided a tractable tool to study how somatic cell identity can be dismantled and pluripotency established. A number of landmark studies have established hallma...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2018.06.002
更新日期：2018-10-01 00:00:00
abstract：:Few mechanistic ideas from the pre-molecular era of biology have had as enduring an impact as the morphogen concept. In the classical view, cells in developing embryos obtain positional information by measuring morphogen concentrations and comparing them with fixed concentration thresholds; as a result, graded morphog...
journal_title：Current opinion in genetics & development
pub_type： 杂志文章,评审
doi：10.1016/j.gde.2011.10.002
更新日期：2011-12-01 00:00:00
