FellowChem. Eng., PhD. Filip Razga
Project NameConjugated Antisense system for Selective and Specific BCR-ABL supprEssion: An innovaTive straTegy for CML trEatment
Host organisationPolymer Institute
Duration of the project07.04.2015 - 06.04.2018

Abstract
Currently, chronic myelogenous leukemia (CML) is widely treated with tyrosine kinase inhibitors (TKIs) that effectively inhibit pro-leukemic activity of the causal BCR-ABL oncoprotein. However, long-term clinical experience with TKIs shows that these drugs are not sufficiently selective and specific for CML cells and BCR-ABL, respectively. This phenomenon often results in clinically significant adverse events responsible for deterioration of TKI treatment outcomes and decreased quality of life. Moreover, limited therapeutic effect of TKIs towards CML stem cells cause that patients with CML are in most of the cases long-term treated, but not completely cured. The development of alternative treatment strategies that exclusively target only CML cells and provide a possibility of permanent cure, is therefore of paramount importance. The proposed Cassette project is dedicated to an innovative antisense concept for effective BCR-ABL silencing. Due to its original design and mechanism of action, the suggested concept allows to significantly enhance both selectivity towards CML cells and sequence-mediated specificity towards BCR-ABL mRNA. It is expected that the presented interdisciplinary effort among the fields of hemato-oncology, organic and macromolecular chemistry will overcome the main issues that have so far hindered introduction of BCR-ABL antisense-therapeutics into clinical practice. Furthermore, as the Cassette system is assumed to be therapeutically effective in any cells containing target mRNA, it has potential to suppress BCR-ABL expression also in CML stem cells, offering thus a hope for permanent cure. If successful, the proposed concept is also expected to provide a tremendous curative potential not only in CML but also in all diseases with known molecular basis, where a particular protein plays a causal role in disease pathophysiology.

Project Summary with Interim Results