Author: Guo, Sheng ; Sun, Wei ; Zhang, Xiaoling ; Yu, Yongli ; Gao, Shuang ; Yan, Youyou ; Wu, Xiuli ; Wang, Hua ; Song, Dandan ; Wang, Luowei ; Li, Hainan ; Wang, Liying

Toll-like receptor 9 (TLR9) can sense pathogen DNA and CpG ODN or even self-DNA by trafficking assisted by Unc93B1, an endoplasmic reticulum (ER) transmembrane protein, from ER to endolysosomes or cell surface. In previous study, we found that an oligodeoxynucleotide with CCT repeats (SAT05f) could selectively inhibit TLR7/9 activation. However, the mechanism for the inhibitory activity of SAT05f is still unknown. In present research, it was found that SAT05f could inhibit CpG ODN-induced the intracellular trafficking of TLR9 and Unc93B1 with feedback the responses of decreased surface TLR9 and enhanced TLR9 mRNA expression but not influence TLR9 protein level by using human plasmacytoid dendritic cell line CAL-1 cells, suggesting that SAT05f inhibits TLR9 activation by restraining TLR9 trafficking. Since the mitochondrial DNA released from injured tissue can cause systemic inflammatory response syndrome (SIRS), this study may provide valuable data for prevention and treatment of SIRS and rescue severe trauma patients.

01 Aug 2012·International ImmunopharmacologyQ2 · MEDICINE

Structure–activity relationship of a guanine-free oligodeoxynucleotide as immunopotent inhibitor

Q2 · MEDICINE

Article

Author: Xiu-Li Wu ; Ying Wang ; Li-Ying Wang ; Yong-Sheng Zhang ; Yong-Li Yu ; Ran Sun

Excessive innate immune response could contribute to the pathogenesis of inflammatory and autoimmune diseases. It is required to develop agents to inhibit the overwhelming innate immune response. SAT05f, an inhibitory ODN with CCT repeat sequence found in human microsatellite DNA, has been demonstrated to down-regulate TLR7/9-mediated innate immune response, protect mice from D-GalN/CpG ODN induced lethal shock, and reduce anti-ssDNA antibody level in the lupus-prone mice induced by chronic graft versus host disease (cGVHD). In this article, to explore the structure-activity relationship of SAT05f, we designed and synthesized a series of ODNs based on the sequence of SAT05f by changing repeat number of the CCT unit, substituting CCT unit with AAG at 3' end or 5' end or in the middle and by forming hairpin at 5' or 3' end, and tested their inhibitory effect on the CpG ODN induced proliferation and TNF-α production in murine immune cells. The results indicated that 1) at least 8 CCT units were required for a CCT repeat ODN to display its inhibitory activity; 2) CCT unit at 3' end of SAT05f was necessary for its full inhibitory activity; and 3) 5' end of SAT05f could be modified to design a more potent SAT05f derived inhibitory ODN. The data provided here would be helpful for finding a potent inhibitory ODN as a candidate medicament for the treatment of diseases associated with over-activated innate immune response.

01 Nov 2011·Biochemical and Biophysical Research CommunicationsQ3 · BIOLOGY

An oligodeoxynucleotide capable of lessening acute lung inflammatory injury in mice infected by influenza virus

Q3 · BIOLOGY

Article

Author: Wenhui Huang ; Ming Yang ; Min Wan ; Sheng Guo ; TieSuo Zhao ; Liying Wang ; Yongli Yu ; Xiuli Wu ; Shucheng Hua ; Ran Sun ; Yongsheng Zhang ; Mingli Fang ; Youyou Yan

Infection of influenza virus could induce acute lung inflammatory injury (ALII) that was at least partially caused by excessive innate immune responses. To study whether down-regulating Toll-like receptor (TLR)-mediated innate immune response could lessen influenza virus-induced ALII, a microsatellite DNA mimicking oligodeoxynucleotide (MS ODN), named as SAT05f capable of inhibiting TLR7/9-activation in vitro, was used to treat mice infected with FM1 virus. In parallel, two MS ODNs confirmed with less or no in vitro activities, named as MS19 and MS33, were used as controls. Unexpectedly, SAT05f failed to lessen ALII in the mice, whereas MS19 significantly inhibited the weight loss and displayed dramatic effect on lessening the ALII by reducing consolidation, hemorrhage, intra-alveolar edema and neutrophils infiltration in lungs of the mice. Meanwhile, MS19 could decrease the mortality of influenza virus infected mice and down-regulate TNF-α production in their lungs. The data suggest that MS19 might display its therapeutic role on ALII induced by influenza virus by reducing over-production of TNF-α.

100 Deals associated with SAT05f

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Immune System Diseases	Preclinical	China	Jilin University	01 Mar 2010

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

SAT05f

Overview

Basic Info

Structure/Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation