Delving into the Latest Updates on Tacere Therapeutics, Inc. with Synapse

Follow-up to Study Protocol B2801001, A Phase I/II, Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of Single Doses of TT-034 in Patients With Chronic Hepatitis C [CHC] Infection

This is a long-term safety follow-up protocol for subjects who received TT-034 under the B2801001 protocol and consists of monitoring for at least 4.5 years.

开始日期2014-11-01

申办/合作机构

Tacere Therapeutics, Inc.

NCT01899092 / Completed临床1/2期

A Phase I,II Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of Single Doses of TT-034 for Subjects With Chronic Hepatitis C (CHC) Infection

The study is a first in man, dose escalation study that will measure the safety and efficacy of TT-034 in the treatment of patients with chronic hepatitis C. The study is divided into 5 dose levels. Subjects will be given a single dose delivered by IV infusion. The subjects will be monitored and the data analyzed. After a set time, between 6 and 10 weeks depending on the dose level, the next set of subjects will be dosed. The study drug is a gene therapy treatment that produces molecules that destroy the Hepatitis C virus (HCV) in infected cells. Once the study drug is given, it cannot be withdrawn. Additionally, once an individual receives a dose, he or she will not be able to receive a second dose, but will remain eligible to receive most other HCV treatments.

开始日期2014-01-01

申办/合作机构

Tacere Therapeutics, Inc.

100 项与 Tacere Therapeutics, Inc. 相关的临床结果

登录后查看更多信息

0 项与 Tacere Therapeutics, Inc. 相关的专利（医药）

登录后查看更多信息

3

项与 Tacere Therapeutics, Inc. 相关的文献（医药）

2014-01-01·Molecular Therapy - Nucleic Acids2区 · 医学

Deep Sequencing Insights in Therapeutic shRNA Processing and siRNA Target Cleavage Precision

2区 · 医学

ArticleOA

作者: Sidders, Benjamin ; Stroud, Tim ; Kennedy, Michael ; Perkins, Hannah ; Lapthorn, Cris ; Corbau, Romu ; Denise, Hubert ; Kinloch, Ross ; Moschos, Sterghios A ; Lavender, Helen ; Fancy, Sally-Ann ; Carter, Nikki ; Burden, Frances ; Suhy, David

TT-034 (PF-05095808) is a recombinant adeno-associated virus serotype 8 (AAV8) agent expressing three short hairpin RNA (shRNA) pro-drugs that target the hepatitis C virus (HCV) RNA genome. The cytosolic enzyme Dicer cleaves each shRNA into multiple, potentially active small interfering RNA (siRNA) drugs. Using next-generation sequencing (NGS) to identify and characterize active shRNAs maturation products, we observed that each TT-034-encoded shRNA could be processed into as many as 95 separate siRNA strands. Few of these appeared active as determined by Sanger 5' RNA Ligase-Mediated Rapid Amplification of cDNA Ends (5-RACE) and through synthetic shRNA and siRNA analogue studies. Moreover, NGS scrutiny applied on 5-RACE products (RACE-seq) suggested that synthetic siRNAs could direct cleavage in not one, but up to five separate positions on targeted RNA, in a sequence-dependent manner. These data support an on-target mechanism of action for TT-034 without cytotoxicity and question the accepted precision of substrate processing by the key RNA interference (RNAi) enzymes Dicer and siRNA-induced silencing complex (siRISC).Molecular Therapy-Nucleic Acids (2014) 3, e145; doi:10.1038/mtna.2013.73; published online 4 February 2014.

2012-03-01·Antimicrobial Agents and Chemotherapy2区 · 医学

In Vitro Characterization of the Activity of PF-05095808, a Novel Biological Agent for Hepatitis C Virus Therapy

2区 · 医学

Article

作者: Lavender, Helen ; Perkins, Hannah ; Corbau, Romu ; Savic, Boris ; Scott, Sarah ; Wright, J. Fraser ; Palmer, Amy ; Smith-Burchnell, Caroline ; Denise, Hubert ; Burden, Frances ; Delpuech-Adams, Oona ; Brady, Kevin ; Troke, Phil ; Suhy, David

ABSTRACT PF-05095808 is a novel biological agent for chronic hepatitis C virus (HCV) therapy. It comprises a recombinant adeno-associated virus (AAV) DNA vector packaged into an AAV serotype 8 capsid. The vector directs expression of three short hairpin RNAs (shRNAs) targeted to conserved regions of the HCV genome. These shRNAs are processed by the host cell into the small interfering RNAs which mediate sequence-specific cleavage of target regions. For small-molecule inhibitors the key screens needed to assess in vitro activity are well defined; we developed new assays to assess this RNA interference agent and so to understand its therapeutic potential. Following administration of PF-05095808 or corresponding synthetic shRNAs, sequence-specific antiviral activity was observed in HCV replicon and infectious virus systems. To quantify the numbers of shRNA molecules required for antiviral activity in vitro and potentially also in vivo , a universal quantitative PCR (qPCR) assay was developed. The number of shRNA molecules needed to drive antiviral activity proved to be independent of the vector delivery system used for PF-05095808 administration. The emergence of resistant variants at the target site of one shRNA was characterized. A novel RNA cleavage assay was developed to confirm the spectrum of activity of PF-05095808 against common HCV clinical isolates. In summary, our data both support antiviral activity consistent with an RNA interference mechanism and demonstrate the potential of PF-05095808 as a therapeutic agent for chronic HCV infection.

2010-09-30·Oncotarget

miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells

Article

作者: Noonan, Emily J. ; Li, Long-Cheng ; Place, Robert F. ; Pookot, Deepa ; Basak, Shashwati

MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) that regulate gene expression by repressing translation or triggering the degradation of complementary mRNA sequences. Certain miRNAs have been shown to function as integral components of the p53 and/or retinoblastoma (Rb) regulatory networks. As such, miRNA dysregulation can have a profound effect on cancer development. Previous studies have shown that miR-449a is down-regulated in human prostate cancer tissue and possesses potential tumor suppressor function. In the present study, we identify miR-449a-mediated growth arrest in prostate cancer cells is dependent on the Rb protein. We show that mutant Rb prostate cancer cells (DU- 145) are resistant to cell cycle arrest and cellular senescence induced by miR- 449a, while overexpression of wild-type Rb in DU-145 sublines (DU-1.1 and B5) restores miR-449a function. In silico analysis of 3'UTR regions reveal a putative miR-449a target site in the transcript of Cyclin D1 (CCND1); an oncogene involved in directly regulating Rb activity and cell cycle progression. Luciferase 3'UTR reporter constructs and inhibitory oligonucleotides confirm that Cyclin D1 is a direct downstream target of miR-449a. We also reveal that miR-449a suppresses Rb phosphorylation through the knockdown of Cyclin D1 and previously validated target HDAC1. By targeting genes involved in controlling Rb activity, miR- 449a regulates growth and senescence in an Rb-dependent manner. These data indicate that miR-449a is a miRNA component of the Rb pathway and its tumor suppressor-like effects, in part, depends on Rb status in prostate cancer cells.

100 项与 Tacere Therapeutics, Inc. 相关的药物交易

登录后查看更多信息

100 项与 Tacere Therapeutics, Inc. 相关的转化医学

登录后查看更多信息