期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/ijms23094804
关键词
G-quadruplex; aptamers; physico-chemical characterization; Huntington's disease; Drosophila melanogaster model
资金
- AIRC [IG2020, 25046, 23198]
- Campania Region [RIS 3-POR FESR 2007/2013, 54-DG 91 n. 403, 15/10/2015]
- Italian Ministry of Economic Development (MiSE)-Fund for Sustainable Development-Call HORIZON2020 PON IC [F/050347/01_03/X32]
- Fondazione Umberto Veronesi
- CNR-Elleva Pharma
- Regione Campania [54-DG 91 n. 403, 15/10/2015, RIS 3-POR FESR 2007/2013-Obiettivo 2.1]
- Inter-University Center for Research in Neurosciences and University of Campania Luigi Vanvitelli
- Naples, Italy
This study identified a guanine-rich aptamer named MS3 that can recognize and modulate the functions of the huntingtin protein with an expanded polyglutamine tract. Experimental results demonstrate that MS3 can effectively internalize and exhibit good efficacy in vivo.
A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington's disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.
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