V160 / Merck (MSD) 
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  • ||||||||||  V160 / Merck (MSD)
    Enhancing the performance of the sterile filtration of vaccines: Proper selection of a prefilter and the role of hydrophobic interactions (Pacific Ballroom: Section 18 (Marriott Marquis San Diego Marina)) -  Jan 28, 2022 - Abstract #ACSSp2022ACS_Sp_10771;    
    Although the sterile filtration of recombinant protein products is relatively straightforward, live attenuated viral (LAV) vaccines with large particle size (100 – 400 nm), such as the cytomegalovirus vaccine, pose significant challenges during sterile filtration with low yields and capacities...Particle yield for the model nanoparticle suspension was also increased by minimizing hydrophobic interactions by adding surfactants like Triton-X 100. This work provides important insights into the factors controlling sterile filtration of large particle vaccines as well as a framework for enhancing the yield and capacity of commercially available sterile filters.
  • ||||||||||  V160 / Merck (MSD)
    Journal:  Evaluation of a Sterile Filtration Process for Viral Vaccines using a Model Nanoparticle Suspension. (Pubmed Central) -  Nov 29, 2021   
    The objectives of this study are to examine the performance of several commercial sterile filters for filtration of a cytomegalovirus vaccine candidate (referred to as the LAV) and to develop and evaluate the use of a model nanoparticle suspension to perform a more quantitative assessment...The particle yield for the Sartobran P was independent of filtrate flux above 200 LMH, but increased with increasing particle concentration, varying from less than 10% at concentrations around 10 particles/ mL to more than 80% at concentrations above 10 particles/ mL due to saturation of particle capture / binding sites within the filter. These results provide important insights into the factors controlling transmission and fouling during sterile filtration of large vaccines.
  • ||||||||||  V160 / Merck (MSD)
    Journal:  Characterization of gH/gL/pUL128-131 pentameric complex, gH/gL/gO trimeric complex, gB and gM/gN glycoproteins in a human cytomegalovirus using automated capillary western blots. (Pubmed Central) -  Aug 15, 2021   
    In our company ongoing Phase II clinical trial of whole-live virus HCMV vaccine (V160), the pentameric gH complex has been restored on the surface of live attenuated AD169 virus strain...This method is suitable for analyzing target proteins in multiple sample types including supernatants from infected cell culture, purification intermediates, concentration bulk, and the final vaccine product. In addition, the capillary western blot-based technology identified a previously unknown biochemical profile present in some HCMV viruses: triplet gH peaks of viral surface proteins in non-reducing environment, which could potentially present a new strategy for specificity and identity testing.
  • ||||||||||  V160 / Merck (MSD)
    Trial completion:  V160 2-Dose and 3-Dose Regimens in Healthy Cytomegalovirus (CMV) Seronegative Females (V160-002) (clinicaltrials.gov) -  Jul 12, 2021   
    P2b,  N=2200, Completed, 
    In addition, the capillary western blot-based technology identified a previously unknown biochemical profile present in some HCMV viruses: triplet gH peaks of viral surface proteins in non-reducing environment, which could potentially present a new strategy for specificity and identity testing. Active, not recruiting --> Completed
  • ||||||||||  V160 / Merck (MSD)
    Journal:  Saturation mutagenesis to improve the degradation of azo dyes by versatile peroxidase and application in form of VP-coated yeast cell walls. (Pubmed Central) -  Nov 12, 2020   
    We used saturation mutagenesis to alter two amino acids in the catalytic tryptophan environment of VP (V160 and A260)...To allow multiple cycles of dye degradation, we immobilized VP on the surface of yeast cells and used washed cell wall fragments after lysis. VP embedded in the cell wall retained ∼70 % of its initial activity after 10 cycles of dye degradation each lasting 12 h, making this platform ideal for the bioremediation of environments contaminated with azo dyes.
  • ||||||||||  V160 / Merck (MSD)
    Journal:  DNA methylation editing by CRISPR-guided excision of 5-methylcytosine. (Pubmed Central) -  Aug 29, 2020   
    We also found that reactivation induced by dCas9-ROS1, as well as that achieved by two different CRISPR-based chromatin effectors (dCas9-VP160 and dCas9-p300), generally decreases with methylation density. Our results suggest that plant 5-meC DNA glycosylases are a valuable addition to the CRISPR-based toolbox for epigenetic editing.
  • ||||||||||  JQ-1 / Roche, V160 / Merck (MSD)
    Preclinical, Journal:  Mouse medulloblastoma driven by CRISPR activation of cellular Myc. (Pubmed Central) -  Oct 11, 2019   
    The BET inhibitor JQ1 suppressed MYC expression in a human G3 MB cell line (HD-MB03) and CRISPR-Myc, but not in Retro-Myc MBs. This G3 MB mouse model in which Myc expression is regulated by its own promoter will facilitate pre-clinical studies with drugs that regulate Myc transcription.
  • ||||||||||  V160 / Merck (MSD)
    Journal:  Targeted Transgene Activation in the Brain Tissue by Systemic Delivery of Engineered AAV1 Expressing CRISPRa. (Pubmed Central) -  May 21, 2019   
    ...To enable AAV packaging, we constructed minimal CRISPRa and CRISPRi transgenes by fusing catalytically inactive Staphylococcus aureus Cas9 (dSaCas9) to the transcriptional activator (VP64 and VP160) and repressor (KRAB and SID4X) domains along with truncated regulatory elements...Importantly, a single-dose intravenous administration of AAV1-PHP.B expressing CRISPRa was shown to achieve targeted transgene activation in the mouse brain. This proof-of-concept study will contribute to the development of a non-invasive, specific and potent AAV-CRISPR system for correcting transcriptional misregulation in broad brain areas and multiple neuroanatomical structures.