کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2121357 1546897 2014 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A rationally designed nanoparticle for RNA interference therapy in B-lineage lymphoid malignancies
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
A rationally designed nanoparticle for RNA interference therapy in B-lineage lymphoid malignancies
چکیده انگلیسی


• CD22ΔE12 is a molecular target for RNA interference (RNAi) therapy in B-lineage lymphoid malignancies.
• A polypeptide-based hybrid nanoparticle formulation of CD22ΔE12-siRNA exhibits anti-leukemic activity.

The purposes of the present study were to further evaluate the biologic significance of the CD22ΔE12 molecular lesion and determine if it could serve as a molecular target for RNA interference (RNAi) therapy. We show that both pediatric and adult B-lineage lymphoid malignancies are characterized by a very high incidence of the CD22ΔE12 genetic defect. We provide unprecedented experimental evidence for a previously unrecognized causal link between CD22ΔE12 and aggressive biology of BPL cells by demonstrating that siRNA-mediated knockdown of CD22ΔE12 in primary BPL cells is associated with a marked inhibition of their clonogenicity. These findings provide the preclinical proof-of-concept that siRNA-mediated depletion of CD22ΔE12 may help develop effective treatments for high-risk and relapsed BPL patients who are in urgent need for therapeutic innovations. We also describe a unique polypeptide-based nanoparticle formulation of CD22ΔE12-siRNA as an RNAi therapeutic candidate targeting CD22ΔE12 that is capable of delivering its siRNA cargo into the cytoplasm of leukemia cells causing effective CD22ΔE12 depletion and marked inhibition of leukemic cell growth. Further development and optimization of this nanoparticle or other nanoformulation platforms for CD22ΔE12-siRNA may facilitate the development of an effective therapeutic RNAi strategy against a paradigm shift in therapy of aggressive or chemotherapy-resistant B-lineage lymphoid malignancies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: EBioMedicine - Volume 1, Issues 2–3, December 2014, Pages 141–155
نویسندگان
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