CD22ΔE12 as a molecular target for RNAi therapy
| Autor: | Jianjun Cheng, Sanjive Qazi, Fatih M. Uckun, Dorothea E. Myers, Hong Ma |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Sialic Acid Binding Ig-like Lectin 2
Gene Expression Mice Transgenic Pharmacology Biology Article Mice In vivo RNA interference Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Gene expression Gene Knockdown Techniques medicine Animals Humans RNA Messenger RNA Small Interfering Molecular lesion Gene knockdown Cancer Genetic Therapy Hematology medicine.disease Xenograft Model Antitumor Assays In vitro Disease Models Animal Liposomes RNA Interference Spleen |
| Zdroj: | British Journal of Haematology. 169:401-414 |
| ISSN: | 0007-1048 |
| Popis: | B-precursor acute lymphoblastic leukaemia (BPL) is the most common form of cancer in children and adolescents. Our recent studies have demonstrated that CD22ΔE12 is a characteristic genetic defect of therapy-refractory clones in paediatric BPL and implicated the CD22ΔE12 genetic defect in the aggressive biology of relapsed or therapy-refractory paediatric BPL. The purpose of the present study is to evaluate the biological significance of the CD22ΔE12 molecular lesion in BPL and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. Here we report a previously unrecognized causal link between CD22ΔE12 and aggressive biology of human BPL cells by demonstrating that siRNA-mediated knockdown of CD22ΔE12 in primary leukaemic B-cell precursors is associated with a marked inhibition of their clonogenicity. Additionally, we report a nanoscale liposomal formulation of CD22ΔE12-specific siRNA with potent in vitro and in vivo anti-leukaemic activity against primary human BPL cells as a first-in-class RNAi therapeutic candidate targeting CD22ΔE12. |
| Databáze: | OpenAIRE |
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