2′‐O,4′‐C‐Ethylene‐Bridged Nucleic Acid (ENA) for Effective Antisense Formation

Morita, Koji; Yamate, Koji; Kurakata, Shinichi; Watanabe, Kenji; Imanishi, Takeshi; Koizumi, Makoto

doi:10.1002/chin.200409198

Cited by 2 publications

(2 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this report we describe our characterization of these TFOs and the influence on bioactivity of these modifications. (25) were purchased from Sankyo Lifetech Co., Ltd. (Tokyo, Japan).…”

mentioning

confidence: 99%

Extensive Sugar Modification Improves Triple Helix Forming Oligonucleotide Activity in Vitro but Reduces Activity in Vivo

et al. 2007

View full text Add to dashboard Cite

We are developing triple helix forming oligonucleotides (TFOs) for gene targeting. Previously, we synthesized bioactive TFOs containing 2'-O-methylribose (2'-OMe) and 2'-O-aminoethylribose (2'-AE) residues. Active TFOs contained four contiguous 2'-AE residues and formed triplexes with high thermal stability and rapid association kinetics. In an effort to further improve bioactivity, we synthesized three series of TFOs containing the 2'-AE patch and additional ribose modifications distributed throughout the remainder of the oligonucleotide. These were either additional 2'-AE residues, the conformationally locked BNA/LNA ribose with a 2'-O,4'-C-methylene bridge, or the 2'-O,4'-C-ethylene analogue (ENA). The additionally modified TFOs formed triplexes with greater thermal stability than the reference TFO, and some had improved association kinetics. However, the most active TFOs in the biochemical and biophysical assays were the least active in the bioassay. We measured the thermal stability of triplexes formed by the TFOs in each series on duplex targets containing a change in sequence at a single position. The Tm value of the variant sequence triplexes increased as the number of all additional modifications increased. A simple explanation for the failure of the improved TFOs in the bioassay was that the increased affinity for nonspecific targets lowered the effective nuclear concentration. Enhancement of TFO bioactivity will require chemical modifications that improve interaction with the specific targets while retaining selectivity against mismatched sequences.

show abstract

“…In this report we describe our characterization of these TFOs and the influence on bioactivity of these modifications. (25) were purchased from Sankyo Lifetech Co., Ltd. (Tokyo, Japan).…”

mentioning

confidence: 99%

Extensive Sugar Modification Improves Triple Helix Forming Oligonucleotide Activity in Vitro but Reduces Activity in Vivo

et al. 2007

View full text Add to dashboard Cite

show abstract

“…In addition to binding affinity, LNA-containing ONs can also increase resistance to degradation by enzymes present both in serum and in the cell. Studies show that introducing at least two LNA nts in the 3´ end of the ON increases protection from 3´ exonuclease activity (117). As with other 2´-modifications, stability can be much enhanced if LNA is combined with PS backbone modification (118,119).…”

Section: Locked Nucleic Acidsmentioning

confidence: 99%

Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs

Gissberg

Zaghloul

Lundin

et al. 2016

Nucleic Acid Therapeutics

View full text Add to dashboard Cite

AS1411 is a g-quadruplex-forming aptamer capable of selectively entering cancer cells by nucleolin receptor-mediated uptake. In this study, we investigated the cell internalization properties and plasticity of AS1411 carrying different locked nucleic acid-containing cargo oligonucleotides (ONs) for delivery into A549 and U2OS cells. We found that internalization efficiency is highly governed by ON cargo chemistry and composition since the inherent antitumor properties of AS1411 were lost when attached to a nontoxic ON, noTox. However, a toxic ON, Tox, demonstrated potent cytotoxicity after aptamer-mediated uptake in A549 cells. We also examined the effect of unlocked nucleic acid (UNA) modifications in the loop region of the aptamer, and how the cargo ONs and UNA incorporation affect the secondary structure of AS1411, in the presence or absence of two novel ellipticine derivatives. These findings add new insights to the design and future applications of aptamer-guided delivery of ON cargo to cancer cells.

show abstract

2′‐O,4′‐C‐Ethylene‐Bridged Nucleic Acid (ENA) for Effective Antisense Formation

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 2 publications

References 1 publication

Extensive Sugar Modification Improves Triple Helix Forming Oligonucleotide Activity in Vitro but Reduces Activity in Vivo

Extensive Sugar Modification Improves Triple Helix Forming Oligonucleotide Activity in Vitro but Reduces Activity in Vivo

Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs

Contact Info

Product

Resources

About