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丁香实验推荐阅读
A Systematic Strategy for the Discovery of Candidate Genes Responsible for Phenotypic Variation

It is increasingly common to combine genome-wide expression data with quantitative trait mapping data to aid in the search for sequence polymorphisms responsible for phenotypic variation. By joining these complex but different data types at the level of the biological pathway, we can ta ...

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Modes of Defining Atherosclerosis in Mouse Models: Relative Merits and Evolving Standards

Mouse models have become the most common model for defining mechanisms of atherosclerotic disease. Many genetic manipulations have enabled the development of atherosclerosis in mice due to either endogenous or diet-induced hypercholesterolemia. This availability of lesion ...

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Evaluating Micro- and Macro-vascular Disease, the End Stage of Atherosclerosis, in Rat Models

Development of effective treatment or, more critically, preventative measures against atherosclerosis and cardiovascular disease will require animal models that mimic the disease processes seen in humans and permit identification of the genetic and physiological factor ...

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Non-invasive Blood Pressure Measurement in Mice

Hypertension is a leading cause of heart attack, stroke, and kidney failure and represents a serious medical issue worldwide. The genetic basis of hypertension is well-established, but few causal genes have been identified thus far. Non-invasive blood pressure measurements are a criti ...

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Direct Blood Pressure Monitoring in Laboratory Rodents via Implantable Radio Telemetry

The ability to monitor and record precise blood pressure fluctuations in research animals is vital to research for human hypertension. Direct measurement of blood pressure via implantable radio telemetry devices is the preferred method for automatic collection of chronic, contin ...

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Measuring Kidney Function in Conscious Mice

Mice lacking or over-expressing a gene of experimental interest have become important tools to understand the regulation of kidney function and water and electrolyte homeostasis. The use of mice in physiological studies is becoming more widespread, but there are still a number of techni ...

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Mouse Surgical Models in Cardiovascular Research

Mouse models that mimic human diseases are important tools for investigating underlying mechanisms in many disease states. Although the demand for these models is high, there are few schools or courses available for surgeons to obtain the necessary skills. Researchers are usually expo ...

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Ischemic Stroke in Mice and Rats

Ischemic stroke occurs most often in the territory of the middle cerebral artery (MCA) in humans. Since its description in rats more than two decades ago, the minimally invasive intraluminal suture occlusion of MCA is an increasingly used model of stroke in both rats and mice due to its ease of inducing ...

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Echocardiographic Examination in Rats and Mice

Rats and mice are the predominant experimental species in cardiovascular research due to the widespread availability of genetic and transgenic rodent models of heart disease. Phenotyping of these models requires reliable and reproducible methods to noninvasively and serially ...

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QTL Mapping in Intercross and Backcross Populations

In the past two decades, various statistical approaches have been developed to identify quantitative trait locus with experimental organisms. In this chapter, we introduce several commonly used QTL mapping methods for intercross and backcross populations. Important issues rel ...

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Evaluation of the Fate of rAAV Genomes Following In Vivo Administration

Recombinant adeno-associated virus (rAAV) vectors are capable of mediating long-term gene expression in a wide variety of animals, including primates. The rAAV genome is packaged into the virion as single-stranded DNA devoid of any viral genes. A proportion of the single-stranded genom ...

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Measuring Immune Responses to Recombinant AAV Gene Transfer

Following AAV-based gene transfer, the occurrence of adaptive immune responses specific to the vector or the transgene product is a major roadblock to successful clinical translation. These responses include antibodies against the AAV capsid, which can be neutralizing and therefo ...

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AAV-Mediated Gene Targeting

The precise alteration of sequences by homologous recombination is an important strategy for gene therapies as well as investigating gene function and cellular DNA repair pathways. Inefficient delivery of template DNA to the nucleus using transfection or electroporation metho ...

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Modification and Labeling of AAV Vector Particles

Adeno-associated virus (AAV) has become a versatile vector platform. In recent years, powerful �techniques for the generation of tropism-modified vectors (rAAV-targeting vectors) and for investigation of virus–cell interaction were developed. The following chapter descr ...

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Preclinical Study Design for rAAV

The process of moving a novel drug such as an adeno-associated viral vector from the bench top to bedside is an arduous process requiring coordination and skill from multiple laboratories and regulatory agencies. Proceeding to a phase I safety trial in humans after most of the proof-of-concept d ...

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Biodistribution and Shedding of AAV Vectors

Determining the AAV vector biodistribution and shedding is central for the safety assessment of proposed early-phase clinical trials. It is especially crucial in the case of AAV vectors since they are injected directly in situ with no possibility of an intermediate ex vivo step, such as in retr ...

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Production and Purification of Recombinant Adeno-Associated Vectors

The use of recombinant adeno-associated virus (rAAV) vectors in gene therapy for preclinical studies in animal models and human clinical trials is increasing, as these vectors have been shown to be safe and to mediate persistent transgene expression in vivo. Constant improvement in rAAV ma ...

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rAAV Vector Product Characterization and Stability Studies

Recombinant adeno-associated viral (rAAV) vectors mediate the safe and long-term correction of genetic diseases following a single administration. Preclinical studies in animal models and human trials have shown rAAV vector persistence and safety. In some trials, sustained or tr ...

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rAAV Human Trial Experience

Recombinant AAV vectors have been used in clinical trials since the mid-1990s, with over 300 subjects enrolled in studies. Although there are not yet licensed AAV products, there are several clear examples of clinical efficacy, and recombinant AAV vectors have a strong safety record after ad ...

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Adeno-Associated Virus Biology

Adeno-associated virus (AAV) was first discovered as a contaminant of adenovirus stocks in the 1960s. The development of recombinant AAV vectors (rAAV) was facilitated by early studies that generated infectious molecular clones, determined the sequence of the genome, and defined the g ...

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