共查询到20条相似文献,搜索用时 0 毫秒
1.
There are more than 40 different forms of inherited lysosomal storage diseases (LSDs) known to occur in humans and the aggregate incidence has been estimated to approach 1 in 7000 live births. Most LSDs are associated with high morbidity and mortality and represent a significant burden on patients, their families, and health care providers. Except for symptomatic therapies, many LSDs remain untreatable, and gene therapy is among the only viable treatment options potentially available. Therapies for some LSDs do exist, or are under evaluation, including heterologous bone marrow transplantation (BMT), enzyme replacement therapy (ERT), and substrate reduction therapy (SRT), but these treatment options are associated with significant concerns, including high morbidity and mortality (BMT), limited positive outcomes (BMT), incomplete response to therapy (BMT, ERT, and SRT), life-long therapy (ERT, SRT), and cost (BMT, ERT, SRT). Gene therapy represents a potential alternative therapy, albeit a therapy with its own attendant concerns. Animal models of LSDs play a critical role in evaluating the efficacy and safety of therapy for many of these conditions. Naturally occurring animal homologs of LSDs have been described in the mouse, rat, dog, cat, guinea pig, emu, quail, goat, cattle, sheep, and pig. In this review we discuss those animal models that have been used in gene therapy experiments and those with promise for future evaluations. 相似文献
2.
Adeno‐associated virus 8‐mediated gene therapy for choroideremia: preclinical studies in in vitro and in vivo models
下载免费PDF全文
![点击此处可从《The journal of gene medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Aaron Black Vidyullatha Vasireddy Daniel C. Chung Albert M. Maguire Rajashekhar Gaddameedi Tania Tolmachova Miguel Seabra Jean Bennett 《The journal of gene medicine》2014,16(5-6):122-130
3.
4.
5.
6.
7.
细菌生物被膜的形成与其致病性、耐药性密切相关,在许多由细菌导致的慢性、亚慢性感染中发挥着重要作用。动物模型广泛应用于细菌生物被膜相关感染的研究中,为其致病机理和控制策略的探究提供了强有力的科学工具。因此,本文系统阐述了哺乳类(鼠、兔、猪等)和非哺乳类(黑腹果蝇、斑马鱼、秀丽隐杆线虫等)动物模型在细菌生物被膜相关研究中的应用,并对动物模型在细菌生物被膜研究中的应用前景进行了展望,以期为研究由生物被膜导致的相关感染而选择理想动物模型提供理论支撑,从而对生物被膜感染导致的潜在危害进行防控。 相似文献
8.
P Briand 《Journal de génétique humaine》1989,37(4-5):289-297
Somatic gene therapies are based on the introduction of genes in somatic cells in an attempt to correct a gene defect, to induce a resistance or to add a particular activity. In their principle, they are not very different from organ grafts and do not set specific ethic problems. Their application to human therapy has to be subjected to a critical evaluation of their harmlessness and efficiency. For this purpose, animal models of somatic gene therapy are essential. Such therapy have been tried in bone marrow and endothelial cells, in fibroblasts, keratinocytes hepatocytes, but also by direct transfer of genes in the organism. These different approaches are briefly reviewed and compared in this article. 相似文献
9.
10.
11.
12.
Katz MG Fargnoli AS Tomasulo CE Pritchette LA Bridges CR 《The journal of gene medicine》2011,13(10):573-586
Heart failure (HF) is a complex multifaceted problem of abnormal ventricular function and structure. In recent years, new information has been accumulated allowing for a more detailed understanding of the cellular and molecular alterations that are the underpinnings of diverse causes of HF, including myocardial ischemia, pressure-overload, volume-overload or intrinsic cardiomyopathy. Modern pharmacological approaches to treat HF have had a significant impact on the course of the disease, although they do not reverse the underlying pathological state of the heart. Therefore gene-based therapy holds a great potential as a targeted treatment for cardiovascular diseases. Here, we survey the relative therapeutic efficacy of genetic modulation of β-adrenergic receptor signaling, Ca(2+) handling proteins and angiogenesis in the most common extrinsic models of HF. 相似文献
13.
BACKGROUND: RNA-based gene silencing is potentially a powerful therapeutic strategy. Catalytic 10-23 DNAzymes bind to target RNA by complimentary sequence arms on a Watson-Crick basis and thus can be targeted to effectively cleave specific mRNA species. However, for in vivo applications it is necessary to stabilise DNAzymes against nucleolytic attack. Chemical modifications can be introduced into the binding arms to increase stability but these may alter catalytic activity and in some cases increase cell toxicity. METHODS: We designed novel 10-23 DNAzyme structures that incorporate stem-loop hairpins at either end on the DNAzyme binding arms. The catalytic activity of hairpin DNAzymes (hpDNAzyme) were tested in vitro against 32P-labelled cRNA encoding the muscle acetylcholine receptor (AChR) alpha-subunit. Resistance of hpDNAzymes to nucleolytic degradation was tested by incubation of the hpDNAzymes with Bal-31, DNase1 or HeLa cell extract. Gene silencing by hpDNAzymes was assessed by measuring reduced fluorescence from DsRed2 and EGFP reporters in cell culture systems, and reduced 125I-alpha-bungarotoxin binding in cells transfected with cDNA encoding the AChR. RESULTS: We show that hpDNAzymes show remarkable resistance to nucleolytic degradation, and demonstrate that in cell culture systems the hpDNAzymes are far more effective than standard 10-23 DNAzymes in down-regulating protein expression from target mRNA species. CONCLUSION: hpDNAzymes provide new molecular tools that, without chemical modification, give highly efficient gene silencing in cells, and may have potential therapeutic applications. 相似文献
14.
15.
We have used a recombinant adenovirus vector (E1−) expressing β-galactosidase to explore a novel mechanism with which to transfer
genes into cells of the central nervous system (CNS). The replication-deficient adenovirus vector expressing β-galactosidase
(RAd35) was propagated on a permissive helper cell line (293 cells). High level protein expression from the human cytomegalovirus
immediate early promoter (hCMV IE) was obtained in a target cell population of RAd35 infected cultured neuronal and glial
cell lines. Light microscopy showed that over 50% of the glial cells studied expressed β-galactosidase. Following retinoic
acid treatment, RAd35 infected cell lines ND7/23, NG108 and NTera2, showed β-galactosidase expression in up to 90% of the
cells. In addition, these cells showed morphological evidence of differentiation into neurons. This pattern of β-galactosidase
expression was also observed in primary rat cerebella granule neuron cultures. In vivo studies were performed in Balb/c mice
following direct intracranial injections of RAd35 into the brain. Cell sections showed a localised staining in the brain at
the site of injection of the virus. Non-replicating adenovirus vectors are therefore highly efficient systems for delivering
a transgene into brain cells. However, their broad cell tropism may limit their applications for genetic disorders in which
a specific cell type is to be targeted for gene therapy. To address this problem, we have constructed adenovirus vectors which
contain specific neuronal promoters and are currently assessing in vitro expression.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
16.
Preclinical cancer vaccine studies must address vaccine safety, immunogenicity, and efficacy, as well as mechanism of vaccine
action. Animal models of vaccines employing human tumor-associated antigen or epitopes (TAA, TAE) differ fundamentally from
those employing tumor-specific antigens or epitopes (TSA, TSE). TSA and TSE vaccines will most likely demonstrate similar
toxicity, immunogenicity, and efficacy in both tumor-bearing animals and patients. In contrast, TAA/TAE immunizations may
have to overcome a host’s immunological tolerance to TAA/TAE expressed not only on tumor, but also on normal tissues; immunity
to TAA/TAE will potentially target normal tissues and thus may induce autoimmunity. Various experimental models for human-derived
TAA/TAE vaccines have been developed. These models include transgenic mice, mice with severe combined immunodeficiency (SCID),
and non-human primates. Recently, unique animal models of TAA/TAE cancer vaccines have been developed, taking advantage of
the discovery of animal tissue antigens with significant sequence homologies to human TAA/TAE. These models mimic perhaps
most closely the situation in cancer patients. 相似文献
17.
Zenildo?Santos Silva Jr Sandra?Kalil Bussadori Kristianne Porta?Santos Fernandes Ying-Ying Huang Michael?R. Hamblin 《Bioscience reports》2015,35(6)
Photodynamic therapy (PDT) employs non-toxic dyes called photosensitizers (PSs), which absorb visible light to give the excited singlet state, followed by the long-lived triplet state that can undergo photochemistry. In the presence of ambient oxygen, reactive oxygen species (ROS), such as singlet oxygen and hydroxyl radicals are formed that are able to kill cancer cells, inactivate microbial pathogens and destroy unwanted tissue. Although there are already several clinically approved PSs for various disease indications, many studies around the world are using animal models to investigate the further utility of PDT. The present review will cover the main groups of animal models that have been described in the literature. Cancer comprises the single biggest group of models including syngeneic mouse/rat tumours that can either be subcutaneous or orthotopic and allow the study of anti-tumour immune response; human tumours that need to be implanted in immunosuppressed hosts; carcinogen-induced tumours; and mice that have been genetically engineered to develop cancer (often by pathways similar to those in patients). Infections are the second biggest class of animal models and the anatomical sites include wounds, burns, oral cavity, ears, eyes, nose etc. Responsible pathogens can include Gram-positive and Gram-negative bacteria, fungi, viruses and parasites. A smaller and diverse group of miscellaneous animal models have been reported that allow PDT to be tested in ophthalmology, atherosclerosis, atrial fibrillation, dermatology and wound healing. Successful studies using animal models of PDT are blazing the trail for tomorrow''s clinical approvals. 相似文献
18.
19.
20.
Aerosol gene therapy 总被引:9,自引:0,他引:9
Gene therapy is a novel field of medicine that holds tremendous therapeutic potential for a variety of human diseases. Targeting
of therapeutic gene delivery vectors to the lungs can be beneficial for treatment of various pulmonary diseases such as lung
cancer, cystic fibrosis, pulmonary hypertension, alpha-1 antitrypsin deficiency, and asthma. Inhalation therapy using formulations
delivered as aerosols targets the lungs through the pulmonary airways. The instant access and the high ratio of the drug deposited
within the lungs noninvasively are the major advantages of aerosol delivery over other routes of administration. Delivery
of gene formulations via aerosols is a relatively new field, which is less than a decade old. However, in this short period
of time significant developments in aerosol delivery systems and vectors have resulted in major advances toward potential
applications for various pulmonary diseases. This article will review these advances and the potential future applications
of aerosol gene therapy technology. 相似文献