Abstract:
:Gene therapy is emerging as a therapeutic modality for treating disorders of the retina. Photoreceptor cells are the primary cell type affected in many inherited diseases of retinal degeneration. Successfully treating these diseases with gene therapy requires the identification of efficient and safe targeting vectors that can transduce photoreceptor cells. One serotype of adeno-associated virus, AAV2, has been used successfully in clinical trials to treat a form of congenital blindness that requires transduction of the supporting cells of the retina in the retinal pigment epithelium (RPE). Here, we determined the dose required to achieve targeting of AAV2 and AAV8 vectors to photoreceptors in nonhuman primates. Transgene expression in animals injected subretinally with various doses of AAV2 or AAV8 vectors carrying a green fluorescent protein transgene was correlated with surgical, clinical, and immunological observations. Both AAV2 and AAV8 demonstrated efficient transduction of RPE, but AAV8 was markedly better at targeting photoreceptor cells. These preclinical results provide guidance for optimal vector and dose selection in future human gene therapy trials to treat retinal diseases caused by loss of photoreceptors.
journal_name
Sci Transl Medjournal_title
Science translational medicineauthors
Vandenberghe LH,Bell P,Maguire AM,Cearley CN,Xiao R,Calcedo R,Wang L,Castle MJ,Maguire AC,Grant R,Wolfe JH,Wilson JM,Bennett Jdoi
10.1126/scitranslmed.3002103subject
Has Abstractpub_date
2011-06-22 00:00:00pages
88ra54issue
88eissn
1946-6234issn
1946-6242pii
3/88/88ra54journal_volume
3pub_type
杂志文章abstract::Retention and use, without explicit parental permission, of residual dried blood samples from newborn screening has generated public controversy over concerns about violations of family privacy rights and loss of parental autonomy. The public debate about this issue has included little discussion a...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3004474
更新日期:2012-11-07 00:00:00
abstract::As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aai8711
更新日期:2017-04-05 00:00:00
abstract::Preclinical data suggest the possibility of repurposing a drug for early intervention in envenoming by snake venom rich in metalloproteinases (Albulescu et al., this issue). ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.abb6700
更新日期:2020-05-06 00:00:00
abstract::A congenital or iatrogenic tissue defect often requires closure by open surgery or metallic components that can erode tissue. Biodegradable, hydrophobic light-activated adhesives represent an attractive alternative to sutures, but lack a specifically designed minimally invasive delivery tool, which limits their clinic...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa2406
更新日期:2015-09-23 00:00:00
abstract::Long synthetic peptides (LSPs) have a variety of important clinical uses as synthetic vaccines and drugs. Techniques for peptide synthesis were revolutionized in the 1960s and 1980s, after which efficient techniques for purification and characterization of the product were developed. These improved techniques allowed ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.3001387
更新日期:2010-09-22 00:00:00
abstract::Sepsis remains a major public health problem with no major therapeutic advances over the last several decades. The clinical and biological heterogeneity of sepsis have limited success of potential new therapies. Accordingly, there is considerable interest in developing a precision medicine approach to inform more rati...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aax9000
更新日期:2019-11-13 00:00:00
abstract::Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detail...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aas9668
更新日期:2018-08-22 00:00:00
abstract::Paving the way for clinical trials, a new study shows that a glutamate receptor antagonist reduces repetitive behavior and social deficits in a mouse model of autism spectrum disorder. ...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.3004017
更新日期:2012-04-25 00:00:00
abstract::We outline the fundamental properties of a highly participatory rapid learning system that can be developed in part from meaningful use of electronic health records (EHRs). Future widespread adoption of EHRs will make increasing amounts of medical information available in computable form. Secured and trusted use of th...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001456
更新日期:2010-11-10 00:00:00
abstract::Beginning with the 18th-century physician-scientist William Heberden, the elder, Science Translational Medicine introduces a new article series about historical figures whose transformational contributions to science, medicine, and society remain relevant today. ...
journal_title:Science translational medicine
pub_type: 历史文章,杂志文章
doi:10.1126/scitranslmed.aaa2250
更新日期:2015-05-13 00:00:00
abstract::Regular physical activity and especially aerobic exercise are associated with reduced risk of disease and enhanced longevity, but the molecular mechanisms of these health benefits remain obscure. A comprehensive metabolomic approach was used to characterize the changes in blood levels of >200 metabolites upon vigorous...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001188
更新日期:2010-07-21 00:00:00
abstract::Clinical proteomics has yielded some early positive results-the identification of potential disease biomarkers-indicating the promise for this analytical approach to improve the current state of the art in clinical practice. However, the inability to verify some candidate molecules in subsequent studies has led to ske...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3001249
更新日期:2010-08-25 00:00:00
abstract::Recent studies have established the involvement of the fat mass and obesity-associated gene (FTO) in metabolic disorders such as obesity and diabetes. However, the precise molecular mechanism by which FTO regulates metabolism remains unknown. Here, we used a structure-based virtual screening of U.S. Food and Drug Admi...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau7116
更新日期:2019-04-17 00:00:00
abstract::Despite the existence of effective rabies vaccines for dogs, dog-transmitted human rabies persists and has reemerged in Africa. Two consecutive dog vaccination campaigns took place in Chad in 2012 and 2013 (coverage of 71% in both years) in the capital city of N'Djaména, as previously published. We developed a determi...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaf6984
更新日期:2017-12-20 00:00:00
abstract::Conventional radiation therapy for cancer usually consists of multiple treatments (called fractions) with low doses of radiation. These dose schemes are planned with the guidance of the linear-quadratic (LQ) model, which has been the most prevalent model for designing dose schemes in radiation therapy. The high-dose f...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3000864
更新日期:2010-07-07 00:00:00
abstract::Systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE) of the skin are autoimmune diseases characterized by inappropriate immune responses against self-proteins; the key elements that determine disease pathogenesis and progression are largely unknown. Here, we show that mice lacking immune inhibitory...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aax1159
更新日期:2019-12-11 00:00:00
abstract::Imaging, including its use for innovative tissue sampling, is slowly being recognized as playing a pivotal role in drug development, clinical trial design, and more effective delivery and monitoring of molecular therapies. The challenge is that, while a considerable number of new imaging technologies and new targeted ...
journal_title:Science translational medicine
pub_type: 杂志文章,评审
doi:10.1126/scitranslmed.aaf3936
更新日期:2016-09-07 00:00:00
abstract::Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction a...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aal1669
更新日期:2017-06-07 00:00:00
abstract::Regulatory T cells (Tregs) are essential to prevent autoimmunity, but excessive Treg function contributes to cancer progression by inhibiting antitumor immune responses. Tregs exert contact-dependent inhibition of immune cells through the production of active transforming growth factor-β1 (TGF-β1). On the Treg cell su...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaa1983
更新日期:2015-04-22 00:00:00
abstract::Glycogen synthase kinase 3 (GSK3), a key regulatory kinase in the wingless-type MMTV integration site family (WNT) pathway, is a therapeutic target of interest in many diseases. Although dual GSK3α/β inhibitors have entered clinical trials, none has successfully translated to clinical application. Mechanism-based toxi...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aam8460
更新日期:2018-03-07 00:00:00
abstract::Accumulating evidence has shown that repeated exposure to general anesthesia during critical stages of brain development results in long-lasting behavioral deficits later in life. To date, there has been no effective treatment to mitigate the neurotoxic effects of anesthesia on brain development. By performing calcium...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aaf7151
更新日期:2016-06-22 00:00:00
abstract::Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translati...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3008234
更新日期:2014-05-28 00:00:00
abstract::Advances in health information technology and electronic medical records have the tremendous potential to accelerate translational and clinical research. However, privacy concerns threaten to be a rate-limiting factor. By recognizing and responding to patient privacy concerns, policy-makers, researchers, and informati...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002037
更新日期:2011-02-09 00:00:00
abstract::In current clinical practice, uterine contractions are monitored via a tocodynamometer or an intrauterine pressure catheter, both of which provide crude information about contractions. Although electrohysterography/electromyography can measure uterine electrical activity, this method lacks spatial specificity and thus...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aau1428
更新日期:2019-03-13 00:00:00
abstract::Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we i...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aag1048
更新日期:2016-09-28 00:00:00
abstract::Antiretroviral therapy has improved the quality and length of life of millions of individuals affected by human immunodeficiency virus type 1 (HIV-1). The capacity of these drugs to indefinitely suppress HIV-which has a well-known capacity for escaping antiviral pressures-is surprising. In this issue of Science Transl...
journal_title:Science translational medicine
pub_type: 评论,杂志文章
doi:10.1126/scitranslmed.3002656
更新日期:2011-07-13 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated wi...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.aad9157
更新日期:2017-05-03 00:00:00
abstract::Therapeutic intravesical instillation of bacillus Calmette-Guérin (BCG) is effective at triggering inflammation and eliciting successful tumor immunity in patients with non-muscle invasive bladder cancer, with 50 to 70% clinical response. Therapeutic success relies on repeated instillations of live BCG administered as...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3003586
更新日期:2012-06-06 00:00:00
abstract::Hutchinson-Gilford progeria syndrome (HGPS) is caused by a point mutation in the LMNA gene that activates a cryptic donor splice site and yields a truncated form of prelamin A called progerin. Small amounts of progerin are also produced during normal aging. Studies with mouse models of HGPS have allowed the recent dev...
journal_title:Science translational medicine
pub_type: 杂志文章
doi:10.1126/scitranslmed.3002847
更新日期:2011-10-26 00:00:00
abstract::About one-third of people in the developed world will undergo cataract surgery in their lifetime. Although marked improvements in surgical technique have occurred since the development of the current approach to lens replacement in the late 1960s and early 1970s, some critical steps of the procedure can still only be ...
journal_title:Science translational medicine
pub_type: 临床试验,杂志文章
doi:10.1126/scitranslmed.3001305
更新日期:2010-11-17 00:00:00