Approaches To Blocking The Immune Response To Gene Transfer With Viral Vectors
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Approaches to Blocking the Immune Response to Gene Transfer with Viral Vectors
Viral vectors are superior tools for gene therapy and as a genetic vaccine platform because viruses have evolved to efficiently infect and transfer their genomes to cells. Several impressive successes in viral vector-based gene therapies have been reported in humans, including restoration of vision in patients with Leber’s congenital amaurosis by retinal gene transfer and cures for severe immune deficiencies by gene transfer to hematopoietic stem cells. However, the mammalian immune system has evolved in parallel to fend off invading pathogens such as viruses. Innate and antigen-specific adaptive immune responses against viral vectors and therapeutic transgene products pose serious hurdles for successful gene therapy. Pre-existing immunity in humans, resulting from prior exposure to the parent virus that forms the basis for the gene transfer vehicle may be derived from, often prevents efficient gene transfer. This problem also reduces our ability to use certain vectors for genetic vaccination or in anti-cancer therapy. For these reasons, the gene transfer community has been extensively studying the mechanisms of immune responses against viral vectors and has started to develop strategies and protocols to block or circumvent such responses. Choice, design and engineering of a vector as well as the route of administration/target tissue can be optimized/ altered to minimize immune responses or evade pre-existing immunity. Immune suppression and modulation strategies are being developed in order to minimize inflammation, prevent antibody or T cell responses against vectors, and to promote tolerance to therapeutic gene products. Combinations of these approaches will likely facilitate clinical applications of gene therapy for many target diseases and also aid in vaccine development.
Adenoviral Vectors for Gene Therapy
Adenoviral Vectors for Gene Therapy provides detailed and comprehensive coverage of these important therapeutic agents. The topics covered in this book range from the basic biology of adenoviruses, through the construction and purification of adenoviral vectors, cutting-edge vectorology and the use of adenoviral vectors in preclinical animal models, to regulatory issues which must be considered prior to the initiation of human clinical gene therapy trials. The broad scope of this unique volume provides the reader with a complete understanding of the development and use of adenoviral vectors. Key Features * Provides complete coverage of basic biology of adenoviruses, as well as the construction, propagation and purification of adenoviral vectors * Introduces common strategies for the development of adenoviral vectors along with cutting-edge methods for their improvement * Demonstrates noninvasive imaging of adenovirus-mediated gene transfer * Discusses utility of adenoviral vectors in animal disease models * Considers Federal Drug Administration regulations for human clinical trials
Cancer Gene Therapy
Author: Nagy Habib
language: en
Publisher: Springer Science & Business Media
Release Date: 2006-04-11
With the coming of the new millennium we are witnessing a revolution in our understanding of cancer genetics. These are very exciting times. Today we have at our disposal the technology to diagnose abnormalities in our cancer genes and the means to correct the deficit and very soon we will have the complete sequence of the human genome. With the use of gene chip technology the way doctors will be able to assess patients will change completely. Today we can diagnose abnormalities in ten thousand genes and within a short period of time we will be able to screen through our genome and discover potential abnormalities in our proto-oncogenes, tumour suppressor genes, differentiating genes, apoptotic genes and pro-inflammatory genes. In this book various authors have highlighted specific genes that could be expressed, overexpressed, neutralised or h- nessed to achieve cancer control. The problem of transferring the therapeutic gene into the cancer cell has been partly addressed with major developments in the field of naked plasmid DNA, adenovirus, retrovirus and adeno-associated viruses. However, further improvements are yet to be made to achieve significant gene transfer. Gene expression, in particular specificity of gene transfer, is obviously an important issue and one which is highlighted in this book by the use of specific promoter.