Specifications

Short turnaround time - Screening turnaround: ONLY 3 weeks

Screening flexibility - Screening parameters can be selected and/or modified based on customer requirements.

Cost effective - A set-up charge applies for the first compound. Subsequent compounds are heavily discounted.

Reliable - Our screening service has been utilized consistently by leading Biotech and Pharmaceutical companies and academic institutes for many years.

Contents

Screening Services

Two choices of services are offered, Compound Profiling and Compound Dose Response, that can be performed sequentially or individually.

• Compound Profiling (level 1): Single dose testing on a set of PRRs.
Screening is performed at a single concentration, typically a 1/10 dilution of the original compound solution provided, or customer specified.

• Compound Dose Response (level 2): Dose response on one or several PRRs
Three concentrations of the compound(s), typically 1/10, 1/100 and 1/1000 dilutions of the original compound solution, are tested on the PRR(s) recognizing the compound(s) as determined in level 1 or specified by the customer.

A detailed report is prepared and provided to the customer electronically and in hard copy. All procedures are performed accordingly to strict guidelines. Confidentiality is guaranteed.

Description

TLR Ligand Screening

The TLR ligand screening service utilizes the HEK-Blue TLR cells.
These HEK293-derived cells are NF-kB-SEAP repor ter cells that stably express a human or mouse TLR gene. The TLR genes expressed are TLR2, 3, 4, 5, 7, 8, and 9.
Compound profiling: The compound is tested on all human and/or mouse TLRs to determine which TLR recognizes this compound. TLR ligands are typically recognized by a single TLR or potentially two (TLR7 and TLR8). Recognition by TLR4 usually reflects the presence of endotoxins in the sample.
Agonist and antagonist assays can be performed.

NOD1/2 Ligand Screening

The NOD1/2 ligand screening service utilizes the HEK-Blue NOD cells.
These HEK-Blue cells stably express an NF-kB-inducible SEAP reporter gene and the human or mouse NOD1 or NOD2 gene.
Compound profiling: The compound is tested on human and/or mouse NOD1 and NOD2.

RIG-I/MDA-5 Ligand Screening

InvivoGen introduces the RIG-I/MDA-5 ligand screening service. This service utilizes recently developed HEK293 cell lines that exploit the IRF pathway and a secreted luciferase reporter assay. They overexpress the human RIG-I or MDA-5 gene and are highly sensitive to 5’ppp-dsRNA and transfected poly(I:C), respectively, unlike their parental cell line that expresses low levels of both RIG-I and MDA-5.
Compound profiling: The compound is tested on human RIG-I and/or MDA-5.

Details

Simplified representation of the TLR, NOD and RLR pathways

Citations

Recent articles using Immunomodulatory Compound Screening

• 2007 - PNAS, 104(47): 18631-18635
  Human {beta}-defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2.
  Funderburg N, Lederman MM, Feng Z, Drage MG, Jadlowsky J, Harding CV, Weinberg A, Sieg SF
  Free article
• 2010 - Blood, 116: 564 - 574
  Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells.
  Schreibelt G, Benitez-Ribas D, Schuurhuis D, Lambeck AJ, van Hout-Kuijer M, Schaft N, Punt CJ, Figdor CG, Adema GJ, de Vries IJ
  Free article
• 2011 - Innate Immunity, 17: 29 - 34
  Expression of NOD2 is increased in inflamed human dental pulps and lipoteichoic acid-stimulated odontoblast-like cells.
  Keller JF, Carrouel F, Staquet MJ, Kufer TA, Baudouin C, Msika P, Bleicher F, Farges JC
  
• 2011 - Clin.Vaccine Immunol., 17: 1356 - 1362
  Poly(Anhydride) Nanoparticles Act as Active Th1 Adjuvants through Toll-Like Receptor Exploitation.
  Tamayo I, Irache JM, Mansilla C, Ochoa-Reparaz J, Lasarte JJ, Gamazo C
  Free article
• 2011 - J. Immunol., 187: 2626 - 2631
  Extracellular Histones Are Mediators of Death through TLR2 and TLR4 in Mouse Fatal Liver Injury.
  Xu J, Zhang X, Monestier M, Esmon NL, Esmon CT