INDEX gene therapy

Council for International Organizations of Medical Sciences (CIOMS). 1990. The Declaration of Inuyama Human Genome Mapping, Genetic Screening and Gene Therapy. Geneva CIOMS. Available at http //www.cioms.ch/index.html [Accessed January 12, 2006]. 

The monodispersity, the large number of surface functionalities, and the unique rheological properties make dendrimers and hyperbranched polymers potential candidates for a variety of applications such as biosensing [249], catalysis [250], gene therapy [251], and lubricant viscosity-index (VI), just to name a few. However, the mechanochemistry of dendrimers and hyperbranched polymers remains little understood. 

Based on these general principles, the first dose in humans should be supported by a single-dose study in an appropriate animal species by the intended clinical route. Several dose levels should be explored, as some gene therapy expression products have a narrow therapeutic index. 

To date, three other APL-associated translocations of the RARa gene have been characterised at the molecular level. The t(5 17)(q35 q21) [96], t(ll 17)(q23 q21) [97, 98] and t(ll 17)(ql3 q21) [99] fuse RARa to Nucleophosmin (NPM), Promyelocytic Leukaemia Zinc Finger (PLZF), and Nuclear Mitotic Apparatus (NuMA) genes, respectively. These translocations result in the expression of chimeric RARa fusion proteins, which all retain the DNA and ligand binding domains of the receptor and gain a dimerization domain from the fusion partner (see Fig. 2 for a schematic representation). So far, the t(5 17)(q35 q21) and t(l I 17)(ql3 q21) have only been reported in index cases and, as with t(15 17)-associated APL, appeared to respond to treatment with ATRA [96,99]. In contrast, APL with t(l I 17)(q23 q21) has been reported on a recurrent basis, albeit at very low frequency, and has consistently been found unresponsive to ATRA therapy [100, 101]. 

---