print small

Participating Countries:

Algeria

Argentina

Australia

Austria

Belgium

Bosnia and Herzegovina

Bulgaria

Croatia

Czech Republic

Denmark

Finland

France

FYR of Macedonia

Germany

Greece

Iceland

Ireland

Israel

Italy

Lithuania

Morocco

Netherlands

New Zealand

Poland

Portugal

Romania

Russian Federation

Serbia

Slovenia

Spain

Sweden

Switzerland

Turkey

Ukraine

United Kingdom

United States

Member area provided by LTFE
COST is supported by the EU Framework Programme Horizon 2020
This website is supported by COST
25/10/2012 (Added to site)
Author(s): Pelofy, S.; Teissie, J.; Golzio, M.; Chabot, S.

Chemically Modified Oligonucleotide–Increased Stability Negatively Correlates with Its Efficacy Despite Efficient Electrotransfer

Journal: Journal of Membrane Biology, 245 (2012), pp. 565-571
DOI: 10.1007/s00232-012-9468-9
Request reprint  |  Tell your friend  | 

Abstract: Despite great potential for disease treatment, small interfering RNA (siRNA) development has been hampered due to its poor stability and the lack of efficient delivery method. To overcome the sensitivity, new generations of chemically modified oligonucleotides have been developed such as the locked nucleic acid (LNA). LNA substitution in an siRNA sequence (siLNA) is supposed to increase its stability and its affinity for its complementary sequence. The purpose of this study was to evaluate the potential benefit of an anti-GFP siLNA using the biophysical delivery method electropermeabilization.Weused two types of electrical conditions: electrochemotherapy (ECT), a condition for efficient transfer of small molecules in clinics, and electrogenotherapy (EGT), a condition for efficient transfer of macromolecules. We first confirmed that siLNA was indeed more stable in mouse serum than unmodified siRNA. After determining the ECT and EGT optimal electrical parameters for a human colorectal carcinoma cell line (HCT-116) expressing eGFP, we showed that modifications of siRNA do not interfere with electrotransfer efficiency. However, despite its higher stability and its high electrotransfer efficacy, siLNA was less efficient for eGFP silencing compared to the electrotransferred, unmodified siRNA regardless of the electrical conditions used. Our study highlighted the care that is needed when designing chemically modified oligonucleotides.



Project Office

Working groups

Steering Committee

Founding members

DC Rapporteurs

Related sites: