Expression, gene therapy products

In gene therapy, production of missing or poorly expressed protein is induced by transferring the coding sequence to the cells in plasmid DNA [223]. In principle, the sequence of any protein can be transferred to the cells for protein production. Regulatory elements of DNA, such as cell specific and inducible promotors, can be... 

The relationship between the dose level of the gene therapy product administered and the level and persistence of transgene expression in specific tissues and any toxicities that are observed should be determined. These data are important to ascertain, as they will affect the clinical monitoring and planned dose escalation in the clinical trials. 

Publications by NIH Clinical Center clinical oncology pharmacists have received national attention and improve pharmacy practice processes examples include ways to standardize expression and nomenclature of cancer treatment regimens " and pharmacy procedures for dealing with gene therapy products. 

In 2005, a nomenclature system for gene therapy products " was developed by WHO within the DSTN framework. This system is based on a two-word scheme. The first word describes the expression gene, and the second word the vector component (see below) ... 

A conventional ADME approach is neither necessary nor appropriate for gene therapy products. However, it is essential to demonstrate the tissue distribution of the vector and the gene. An extensive evaluation of tissue distribution may be inappropriate due to methodological difficulties, but it is important to demonstrate that expression of the gene has occurred in tissues in which no adverse effects have been observed. 

Assessment of the immimogenic consequences of gene delivery should also be possible in the chosen species this is particularly important for the evaluation of viral vectors. There has been much discussion on the value of using a permissive host to assess potential human risk from these vectors. The natural route of exposure - i.e. respiratory for adenoviruses - traditionally used to assess permissivity, seems unnecessary to assess the safety of gene therapy products, particularly with the core study approach discussed above. Systemically-administered replication-competent adenovirus will infect (i.e. gain entry into the cell) and be pathogenic in numerous tissues (Duncan et al., 1978). Gene expression and viral replication depend on the species, route of exposure, and individual tissue susceptibility (Torres et al., 1996 Bett et al., 1962). Thus i.v. administration of viral vectors to mammalian test species should permit the evaluation of potential toxicity of widely-distributed vectors. 

It is not possible or desirable to identify a recipe for the safety studies that should be conducted with gene therapy products to support either the first dose in humans or extended clinical evaluation. Each product should be treated on a case-by-case basis, taking into consideration a number of important factors, including the clinical indication, the duration of expression of the gene, and whether DNA transfer will be in vivo or ex vivo. 

Gene Expression Analysis Gene Gun Gene Products Gene Promoter Gene Therapy Gene-therapy Vectors Gene Transfer... 

---