4.6 Article

Synthesis and Exon-Skipping Properties of a 3′-Ursodeoxycholic Acid-Conjugated Oligonucleotide Targeting DMD Pre-mRNA: Pre-Synthetic versus Post-Synthetic Approach

Journal

MOLECULES
Volume 26, Issue 24, Pages -

Publisher

MDPI
DOI: 10.3390/molecules26247662

Keywords

antisense oligonucleotide; conjugation; bile acid; ursodeoxycholic acid; solid support; solid phase synthesis; exon-skipping; dystrophin

Ask authors/readers for more resources

The study found that ASO oligonucleotides conjugated with ursodeoxycholic acid (UDCA) showed better performance in targeting human DMD exon 51 compared to unconjugated ones, with an average 9.5-fold increase in exon skipping efficiency.
Steric blocking antisense oligonucleotides (ASO) are promising tools for splice modulation such as exon-skipping, although their therapeutic effect may be compromised by insufficient delivery. To address this issue, we investigated the synthesis of a 20-mer 2 '-OMe PS oligonucleotide conjugated at 3 '-end with ursodeoxycholic acid (UDCA) involved in the targeting of human DMD exon 51, by exploiting both a pre-synthetic and a solution phase approach. The two approaches have been compared. Both strategies successfully provided the desired ASO 51 3 '-UDC in good yield and purity. It should be pointed out that the pre-synthetic approach insured better yields and proved to be more cost-effective. The exon skipping efficiency of the conjugated oligonucleotide was evaluated in myogenic cell lines and compared to that of unconjugated one: a better performance was determined for ASO 51 3 '-UDC with an average 9.5-fold increase with respect to ASO 51.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available