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Development of aptamers for research, imaging and therapy of neurodegenerative diseases

Développement d’aptamères pour l’étude, l’imagerie et la thérapie des maladies neurodégénératives

​Responsable : Frédéric Ducongé

Published on 23 November 2018

EMAIL : Frédéric Ducongé

Development of new probes for specific molecular recognition

For several years, we have been developing innovative methods for the selection of aptamers that have led to several patents. Our aim is to use these aptamers to study the mechanisms involved in neurodegenerative diseases and to develop new therapeutic and diagnostic approaches.

Structure aptamere.jpg
Modeled structure of an aptamer

Aptamers are high affinity ligands made up of three-dimensional structures of nucleic acids (RNA, DNA or modified chemistry). They can be selected by in vitro molecular evolution methods against many molecular targets (e. g. proteins, peptides or small chemical molecules such as metabolites or neurotransmitters). Aptamers have several advantages over antibodies. For example, they can be chemically produced and are very stable over a wide range of pH and temperature. They can thus be easily combined with many compounds to create new specific molecular recognition probes.   

Microscopie-aptamere.pngInternalization of an anti-Annexin A2 aptamer in cells visualized by Fluorescence microscopy. The aptamer, marked in red, binds rapidly to the cell surface and is internalized over time. (PLoS ONE 9(1): e87002.).


Our research activity concerns:

1- the selection of aptamers that can specifically recognize different types of protein aggregates involved in neurodegenerative diseases.

2- the selection of aptamers that can be used for in vivo imaging of gene expression.

3- the selection of aptamers that can inhibit proteins involved in neuronal death.


Laboratory Members Associated with Projects

  • Alix Bouvier-Müller (PhD Student) - Fellowship IRTELIS CEA. 2016-2019.
  • Cynthia Forier (Engineer) - Contrat CDD CEA. 2017-2019
  • Yann Bramoulle (Researcher)
  • Alexis Bemelmans (Researcher)
  • Nadja Van Camp (Researcher)
  • Thibault Percerou (Technician)
  • Gwenaëlle Aurégan (Technician)
  • Emmanuel Brouillet (DR2-CNRS)
  • Philippe Hantraye (DR2-CNRS)

 

Main collaborations

  • Ronald Melki, Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
  • LFB Biotechnologies, les Ulis, France

 

Recent publications

Nucleic acid aptamers for neurodegenerative diseases
Bouvier-Müller, A. and Ducongé, F. 
Biochimie 2017 j.biochi.2017.10.026.

DNA aptamer affinity ligands for highly selective purification of human plasma-related proteins from multiple sources
Forier, C., Boschetti, E., Ouhammouch, M., Cibiel, A., Duconge, F., Nogre, M., Tellier, M., Bataille, D., Bihoreau, N., Santambien, P. et al. 
J Chromatogr 2017 A, 1489, 39-50.

Applications of High-Throughput Sequencing for In Vitro Selection and Characterization of Aptamers
Nguyen Quang, N., Perret, G. and Ducongé, F. 
Pharmaceuticals 2016, 9, 76.

How to Measure the Affinity of Aptamers for Membrane Proteins Expressed on the Surface of Living Adherent Cells
Quang, N.N., Pestourie, C., Cibiel, A. and Duconge, F. 
Methods 2016, 97, 35-43.

In Vitro and In Vivo Imaging of Fluorescent Aptamers
Theodorou, I., Quang, N.N., Gombert, K., Theze, B., Lelandais, B. and Duconge, F. 
Methods Mol Bio 2016, 1380, 135-150.1.