Abstract:
:Several neurological disorders may benefit from gene therapy. However, even when using the lead vector candidate for intrathecal administration, adeno-associated virus serotype 9 (AAV9), the strength and distribution of gene transfer to the brain are inconsistent. On the basis of preliminary observations that standard intrathecal AAV9 infusions predominantly drive reporter gene expression in brain regions where gravity might cause cerebrospinal fluid to settle, we tested the hypothesis that counteracting vector "settling" through animal positioning would enhance vector delivery to the brain. When rats are either inverted in the Trendelenburg position or continuously rotated after intrathecal AAV9 infusion, we find (i) a significant 15-fold increase in the number of transduced neurons, (ii) a marked increase in gene delivery to cortical regions, and (iii) superior animal-to-animal consistency of gene expression. Entorhinal, prefrontal, frontal, parietal, hippocampal, limbic, and basal forebrain neurons are extensively transduced: 95% of transduced cells are neurons, and greater than 70% are excitatory. These findings provide a novel and simple method for broad gene delivery to the cortex and are of substantial relevance to translational programs for neurological disorders, including Alzheimer's disease and related dementias, stroke, and traumatic brain injury.
journal_name
Sci Advjournal_title
Science advancesauthors
Castle MJ,Cheng Y,Asokan A,Tuszynski MHdoi
10.1126/sciadv.aau9859subject
Has Abstractpub_date
2018-11-14 00:00:00pages
eaau9859issue
11issn
2375-2548pii
aau9859journal_volume
4pub_type
杂志文章相关文献
Science Advances文献大全abstract::Poor transport of neuropharmaceutics through central nervous system (CNS) barriers limits the development of effective treatments for CNS disorders. We present the facile synthesis of a novel neuroinflammation-targeting polyethylene glycol-based dendrimer (PEGOL-60) using an efficient click chemistry approach. PEGOL-6...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay8514
更新日期:2020-01-22 00:00:00
abstract::Earthquake forecasting is the ultimate challenge for seismologists, because it condenses the scientific knowledge about the earthquake occurrence process, and it is an essential component of any sound risk mitigation planning. It is commonly assumed that, in the short term, trustworthy earthquake forecasts are possibl...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1701239
更新日期:2017-09-13 00:00:00
abstract::Quantum phenomena have the potential to speed up the solution of hard optimization problems. For example, quantum annealing, based on the quantum tunneling effect, has recently been shown to scale exponentially better with system size than classical simulated annealing. However, current realizations of quantum anneale...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1602273
更新日期:2017-04-07 00:00:00
abstract::V1-ATPase is an ATP-driven rotary motor that is composed of a ring-shaped A3B3 complex and a central DF shaft. The nucleotide-free A3B3 complex of Enterococcus hirae, composed of three identical A1B1 heterodimers, showed a unique asymmetrical structure, probably due to the strong binding of the N-terminal barrel domai...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aau8149
更新日期:2019-01-30 00:00:00
abstract::Cyclosporine A (CsA) is a powerful immunosuppressant, but it is an ineffective stand-alone treatment for systemic lupus erythematosus (SLE) due to poor target tissue distribution and renal toxicity. We hypothesized that CD71 (transferrin receptor 1)-directed delivery of CsA to the lymphatic system would improve SLE ou...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb3900
更新日期:2020-06-12 00:00:00
abstract::Biogenesis in prokaryotes and eukaryotes requires the insertion of α-helical proteins into cellular membranes for which they use universally conserved cellular machineries. In bacterial inner membranes, insertion is facilitated by YidC insertase and SecYEG translocon working individually or cooperatively. How insertas...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aau6824
更新日期:2019-01-30 00:00:00
abstract::Cost-benefit trade-offs for individuals participating in social behaviors are the basis for current theories on the evolution of social behaviors and societies. However, research on social strategies has largely ignored solitary animals, in which we assume that rare interactions are explained by courtship or territori...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1701218
更新日期:2017-10-11 00:00:00
abstract::Previous identification of the inducible nitric oxide synthase (NOS2) gene as a risk allele for psoriasis (Ps) and psoriatic arthritis (PsA) suggests a possible pathogenic role of nitric oxide (NO). Using a mouse model of mannan-induced Ps and PsA (MIP), where macrophages play a regulatory role by releasing reactive o...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aas9864
更新日期:2018-05-16 00:00:00
abstract::The ability of a material to adopt multiple structures, known as polymorphism, is a fascinating natural phenomenon. Various polymorphs with unusual properties are routinely synthesized by compression under positive pressure. However, changing a material's structure by applying tension under negative pressure is much m...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaq1442
更新日期:2018-04-20 00:00:00
abstract::A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensu...
journal_title:Science advances
pub_type: 杂志文章,评审
doi:10.1126/sciadv.aax0903
更新日期:2019-07-24 00:00:00
abstract::In the healthy kidney, specialized cells called podocytes form a sophisticated blood filtration apparatus that allows excretion of wastes and excess fluid from the blood while preventing loss of proteins such as albumin. To operate effectively, this filter is under substantial hydrostatic mechanical pressure. Given th...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aap8030
更新日期:2018-06-27 00:00:00
abstract::Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-γ (IFN-γ), in offspring's brains play a central role. IFN-γ activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-γ is implicated in brain development. We tested th...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay9506
更新日期:2020-08-19 00:00:00
abstract::Bioengineered three-dimensional (3D) matrices expand our experimental repertoire to study tumor growth and progression in a biologically relevant, yet controlled, manner. Here, we used peptide amphiphiles (PAs) to coassemble with and organize extracellular matrix (ECM) proteins producing tunable 3D models of the tumor...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb3298
更新日期:2020-10-02 00:00:00
abstract::Helicobacter pylori is a leading cause of peptic ulceration and gastric cancer worldwide. To achieve colonization of the stomach, this Gram-negative bacterium adheres to Lewis(b) (Le(b)) antigens in the gastric mucosa using its outer membrane protein BabA. Structural information for BabA has been elusive, and thus, it...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1500315
更新日期:2015-08-14 00:00:00
abstract::Redox flow batteries (RFBs) are considered one of the most promising large-scale energy storage technologies. However, conventional RFBs suffer from low energy density due to the low solubility of the active materials in electrolyte. On the basis of the redox targeting reactions of battery materials, the redox flow li...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1500886
更新日期:2015-11-27 00:00:00
abstract::Donkeys and horses share a common ancestor dating back to about 4 million years ago. Although a high-quality genome assembly at the chromosomal level is available for the horse, current assemblies available for the donkey are limited to moderately sized scaffolds. The absence of a better-quality assembly for the donke...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaq0392
更新日期:2018-04-04 00:00:00
abstract::Cholesterol-dependent cytolysins (CDCs) form pores in cholesterol-rich membranes, but cholesterol alone is insufficient to explain their cell and host tropism. Here, we show that all eight major CDCs have high-affinity lectin activity that identifies glycans as candidate cellular receptors. Streptolysin O, vaginolysin...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaz4926
更新日期:2020-05-22 00:00:00
abstract::Local thermal magnetization fluctuations in Li-doped MnTe are found to increase its thermopower α strongly at temperatures up to 900 K. Below the Néel temperature (TN ~ 307 K), MnTe is antiferromagnetic, and magnon drag contributes αmd to the thermopower, which scales as ~T3. Magnon drag persists into the paramagnetic...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aat9461
更新日期:2019-09-13 00:00:00
abstract::A withdrawal-associated impairment in β-endorphin neurotransmission in the arcuate nucleus (ARC) of the hypothalamus is associated with alcohol dependence characterized by a chronic relapsing disorder. Although acupuncture activates β-endorphin neurons in the ARC projecting to the nucleus accumbens (NAc), a role for A...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aax1342
更新日期:2019-09-04 00:00:00
abstract::SWI/SNF (switch/sucrose nonfermenting) complexes regulate transcription through chromatin remodeling and opposing gene silencing by Polycomb group (PcG) proteins. Genes encoding SWI/SNF components are critical for normal development and frequently mutated in human cancer. We characterized the in vivo contributions of ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay3823
更新日期:2020-05-20 00:00:00
abstract::The investigation of materials that exhibit quantum phase transition provides valuable insights into fundamental problems in physics. We present neutron scattering under pressure in a triangular-lattice antiferromagnet that has a quantum disorder in the low-pressure phase and a noncollinear structure in the high-press...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaw5639
更新日期:2019-10-18 00:00:00
abstract::Bones adapt to mechanical forces according to strict principles predicting straight shape. Most bones are, however, paradoxically curved. To solve this paradox, we used computed tomography-based, four-dimensional imaging methods and computational analysis to monitor acute and chronic whole-bone shape adaptation and re...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aax8301
更新日期:2020-03-06 00:00:00
abstract::Copper-containing nitrite reductases (CuNiRs), encoded by nirK gene, are found in all kingdoms of life with only 5% of CuNiR denitrifiers having two or more copies of nirK Recently, we have identified two copies of nirK genes in several α-proteobacteria of the order Rhizobiales including Bradyrhizobium sp. ORS 375, en...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abd8523
更新日期:2021-01-01 00:00:00
abstract::The degradation of cadmium sulfide (CdS)-based oil paints is a phenomenon potentially threatening the iconic painting The Scream (ca. 1910) by Edvard Munch (Munch Museum, Oslo) that is still poorly understood. Here, we provide evidence for the presence of cadmium sulfate and sulfites as alteration products of the orig...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aay3514
更新日期:2020-05-15 00:00:00
abstract::Artificial liquid-repellent surfaces have attracted substantial scientific and industrial attention with a focus on creating functional topological features; however, the role of the underlying structures has been overlooked. Recent developments in micro-nanofabrication allow us now to construct a skin-muscle type sys...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aba9721
更新日期:2020-08-05 00:00:00
abstract::Earth's night sky continuously produces a faint chemiluminescence known as nightglow. Two prominent nighttime emissions around 90 km are the O2 Atmospheric and the OH Meinel band systems. Despite a plethora of studies since their identification seven decades ago, substantial gaps persist in our understanding of the me...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aau9255
更新日期:2019-03-20 00:00:00
abstract::Many applications in modern technology, such as self-cleaning surfaces and digital microfluidics, require control over individual fluid droplets on flat surfaces. Existing techniques may suffer from side effects resulting from high electric fields and high temperatures. Here, we introduce a markedly different method, ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aaw0914
更新日期:2019-06-14 00:00:00
abstract::Despite the important roles that horses have played in human history, particularly in the spread of languages and cultures, and correspondingly intensive research on this topic, the origin of domestic horses remains elusive. Several domestication centers have been hypothesized, but most of these have been invalidated ...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.abb0030
更新日期:2020-09-16 00:00:00
abstract::The control and use of light polarization in optical sciences and engineering are widespread. Despite remarkable developments in polarization-resolved imaging for life sciences, their transposition to strongly scattering media is currently not possible, because of the inherent depolarization effects arising from multi...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.1600743
更新日期:2017-09-01 00:00:00
abstract::The design of single-molecule photoswitchable emitters was the first milestone toward the advent of single-molecule localization microscopy, setting a new paradigm in the field of optical imaging. Several photoswitchable emitters have been developed, but they all fluoresce in the visible or far-red ranges, missing the...
journal_title:Science advances
pub_type: 杂志文章
doi:10.1126/sciadv.aax1166
更新日期:2019-09-27 00:00:00