Choosing Targets for Gene Therapy
Year: 2011
Type: book-chapter
Abstract: Gene therapy is often attempted in fatal diseases with no known cure, or after standard therapies have failed. Targeting gene defects includes addressing a single mutation, multiple mutations in several genes, or even addressing missing or extra copies in a particular disease. A defect in one specific gene may impair normal function of the corresponding expressed protein. For example, in X-linked severe combined immunodeficiency (X-SCID), there is a mutation in the IL2 receptor ┛ gene. Another classic example occurs in thalassemia propagated by a defect in the ┚-globulin gene. Some diseases are caused by multiple mutations in several genes. For example, some cardiovascular diseases may manifest due to mutations in different chromosomes which are a result of inherited or environmental factors. Before approaching a disease using gene therapy, the key protein(s) and pathways involved in the disease should first be identified. However, in some cases an abnormal gene is formed that results in disease; such is the case for the BcrAbl gene. The oncogenic Bcr-Abl protein is the causative agent of chronic myelogenous leukemia (CML) which could be blocked for CML treatment. Genomic sequencing information, microarrays, and biochemical assays can be used to determine upor downregulated proteins involved in disease, and will help determine the function of these proteins. In the case of some cancers, the signal transduction pathways for oncogenesis have been mapped out, allowing hub proteins to be identified. Hub proteins are essential proteins that interact with multiple other proteins in signaling cascades. If selected properly, adding back a tumor-suppressing hub protein (such as p53), or blocking an oncogenic hub protein (such as survivin) could halt cancer or alter disease progression. Gene mutations can result in mislocalization of these key proteins which can cause cancer; this mislocalization can be exploited with gene therapy approaches. Further, new types of gene therapy are being developed in our lab to direct proteins to other cellular compartments where their function is altered. This chapter will summarize these and other known targets and also focus on choosing newer targets for gene therapy.
Source: InTech eBooks
DOI: 10.5772/22528
Authors: Karina J., Ruben R., James R., Carol S.
Institution: University of Utah
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W1546136260