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Oligonucleotides targeted against a junction oncogene are made efficient by nanotechnologies
Andrei Maksimenko1, Claude Malvy, Gregory Lambert
1CNRS UMR 1582, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif cedex, France.
Pharmaceutical Research
|November 19, 2003
Summary
Antisense oligonucleotides (AON) targeting the EWS-Fli-1 oncogene show promise for Ewing Sarcoma treatment. Nanotechnology delivery systems, including nanocapsules and nanospheres, significantly improved AON efficacy in vivo.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Antisense oligonucleotides (AON) targeting the EWS-Fli-1 oncogene are a potential therapeutic strategy for Ewing Sarcoma.
- Previous in vivo applications of AONs were limited by degradation and poor cellular uptake.
Purpose of the Study:
- To enhance the in vivo delivery and efficacy of AONs against the EWS-Fli-1 oncogene using nanotechnology.
- To evaluate nanocapsules and nanospheres as delivery vehicles for AONs.
Main Methods:
- Two distinct AONs targeting the EWS-Fli-1 fusion gene were synthesized and formulated.
- Nanocapsules delivered a phosphorothioate AON, while nanospheres delivered a modified chimeric AON.
- Formulations were administered intratumorally to nude mice bearing EWS-Fli-1 tumors, with tumor volume monitored and mRNA levels analyzed via Northern blot.
Main Results:
- Nanoparticle-delivered AONs specifically inhibited the growth of EWS-Fli-1 dependent tumors in vivo.
- The study demonstrated a significant downregulation of EWS-Fli-1 mRNA, confirming the antisense effect.
- Nanocapsules and nanospheres proved effective in overcoming previous limitations of AON delivery.
Conclusions:
- Both nanocapsules and nanospheres represent promising nanotechnology-based systems for effective in vivo delivery of AONs.
- These findings support the potential of nanotechnology to enable AON-based therapies for Ewing Sarcoma.