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2009:
Asadi-Moghaddam Kaveh; Chiocca E Antonio
Gene- and viral-based therapies for brain tumors.
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 2009;
6(
3):.
Advances in understanding and controlling genes and their expression have set the stage to alter genetic material to fight or prevent disease with brain tumors being among one of the first human malignancies to be targeted by gene therapy. All proteins are coded for by DNA and most neoplastic diseases ultimately result from the expression or lack thereof with one or more proteins (e.g., coded by oncogenes or tumor suppressor genes, respectively). In theory, therefore, diseases could be treated by expression of the appropriate protein in the affected cells. Gene therapy is an experimental treatment that involves introducing genetic material (DNA or RNA) into cells, and it has made important advances in the past decade. Within this short time span, it has moved from the conceptual laboratory research stage to clinical translational trials for brain tumors. The most efficient approaches for gene delivery are based on viral vectors, which have been proven relatively safe in the CNS, despite occasional cases of morbidity and death in non-neurosurgical trials. However, the human response to various viral vectors can not be predicted in a reliable manner from animal experimentation, nor can size, consistency, and extent of experimental brain tumors in mouse models reflect the large, necrotic, infiltrative nature of malignant gliomas. Furthermore, the problem of delivering genetic vectors into solid brain tumors and the efficiency in situ gene transfer remains one of the most significant hurdles in gene therapy.
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