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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
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Modulation of BACE1 Activity by Chemically Modified Aptamers.
Cécile Gasse1, Marwa Zaarour1, Sam Noppen2
1Univ Evry, CNRS-UMR8030-Laboratoire iSSB, CEA, DRF, IG, Genoscope, Université Paris-Saclay, 5 rue Henri Desbruères, Évry, 91030, France.
Chembiochem : a European Journal of Chemical Biology
|January 13, 2018
Summary
Researchers developed a modified DNA aptamer targeting BACE1, crucial in Alzheimer's disease. This novel aptamer effectively binds and inhibits BACE1 activity, showing promise for therapeutic development.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Alzheimer's disease is a neurodegenerative disorder.
- Beta-secretase 1 (BACE1) is a key therapeutic target for Alzheimer's disease.
- Aptamers are short nucleic acid sequences with high specificity for molecular targets.
Purpose of the Study:
- To develop a modified DNA aptamer with enhanced binding and inhibitory properties against BACE1.
- To investigate the efficacy of nucleobase modifications in aptamer function.
Main Methods:
- In vitro selection (SELEX) was employed to identify functional aptamers.
- Two nucleobase modifications, 5-chlorouracil and 7-deazaadenine, were incorporated.
- The binding affinity and protease inhibition activity of the modified aptamer were evaluated in vitro.
Main Results:
- A modified DNA aptamer that tightly binds BACE1 was successfully developed.
- The aptamer demonstrated significant inhibition of BACE1 protease activity in vitro.
- The inhibitory range was comparable to previously described unmodified aptamers.
Conclusions:
- Modified DNA aptamers represent a promising therapeutic strategy for Alzheimer's disease.
- Nucleobase modifications, specifically 5-chlorouracil, can enhance aptamer functionality.
- Further research into in vivo applications of these modified aptamers is warranted.
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