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CAR-T cells have yielded unprecedented efficacy in B cell malignancies, most remarkably anti-CD19 CAR-T cells for B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate.

The ability to rewire our own immune system to fight cancer has certainly created huge expectations. After the success, more and more preclinical experiments and Phase I-III trials will be performed on large groups. The distribution of CAR-T cells and Oncolytic Viruses in the tumor and in the body is important for assessing the antitumor effect and safety of the injected CAR-T or Oncolytic Viruses in vivo, while observing the antitumor effect. Because of the heterogeneity of the tumor, the in situ localization and distribution of CAR-T cells and oncolytic virus in tumor cells and tumor microenvironment can reflect the mechanism and application prospect of the treatment method.

As CAR-T and oncolytic viruses themselves carry their own unique nucleic acid sequences, RNA specific probes designed for these regions can effectively detect the distribution of these cells or viruses in situ. So RNA ISH is a unique and effective tool for detecting CAR T cells and viruses in situ.

With years of professional experience in the RNA ISH Probe and ISH Service field, Creative Bioarray's streamlined process can offer timely and dependable in situ detection of CAR-T and Oncolytic Viruses results, giving you the flexibility to focus on other research priorities.

Applications

  • In Situ detect the distribution of CAR-T cells/Oncolytic Viruses in tumor cells or tissues
  • Assess the antitumor effect and safety of the injected CAR-T or Oncolytic Viruses in vivo
  • Confirm CAR expression in FFPE tissue
  • Quantify the CAR expression in FFPE tissue

Features

  • Accurate-In Situ Detection Service-Custom design your probe
  • Value – We focus on the quality of our service and all supported by competitive pricing
  • Efficiency – We are able to provide the fastest turnaround time of any supplier in the industry
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Creative Bioarray is an experienced and outstanding provider of cell-based Screening and profiling Services including cell-based high-throughput and high-content screening, specificity and selectivity profiling, and dose-response analysis. With our experienced scientific team and advanced technologies, we are able to quickly narrow down a large pool of candidates and identify effective compounds.

Cell-based screening, as a broad, system biology approach, has the advantage of testing the effects of compounds within the context of living cells, thus helps deliver more effective and safer drugs. New automated technologies have emerged and are available for cell-based screening and profiling. Data obtained from those assays offers a comprehensive view of the overall cellular responses caused by the tested compounds, enabling a more integrated decision regarding to lead generation and optimization.

Our cell-based screening and profiling services include:

  • High-Throughput Screening
  • High-Content Screening
  • Specificity Profiling
  • Selectivity Profiling
  • Dose-Response Analysis
  • Customized Services

Creative Bioarray has worked in this field for years and has extensive experience in drug discovery. We are dedicated to providing data of the highest quality for our customers and helping accelerate the drug discovery process. Do not hesitate to contact us for more information.

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Inflammation and autoimmune is a physiological phenomenon by which the white blood cells and the substances they produce to against foreign organisms (such as bacteria and viruses). However, in some cases, the immune system can also trigger an inflammatory response without foreign invasion. In these inflammation and autoimmune diseases, the tissues are often damaged by their own immune systems. And the whole body reacts as if it were infected by a foreign organism.

To develop drugs against such diseases, researchers typically avoid harming patients and instead use animal disease models. We provide a number of validated models of inflammatory and autoimmune diseases, including arthritis, psoriasis, colitis, and immune disease (CIA, DTH, PCA, EAE). Each disease type has a different model that provides different disease parameters for your candidate compounds.

Our inflammatory and autoimmune disease models can serve as the assay basis for analysis of biomarkers and provide accurate experimental capabilities to elucidate the role of candidate compounds in the treatment of each disease.

Our Inflammation and Autoimmune Disease Models including:

  • Rheumatoid arthritis models
  • Glomerulonephritis models
  • Multiple sclerosis (MS) models
  • Ocular inflammation models
  • Sjögren's syndrome models
  • LPS-induced acute lung injury models
  • Peritonitis models
  • Passive cutaneous anaphylaxis models
  • Delayed-type hypersensitivity (DTH) models
  • Inflammatory bowel disease models
  • Systemic lupus erythematosus animal models
  • Oral mucositis model
  • Asthma model
  • Sepsis model
  • Psoriasis model
  • Atopic dermatitis (AD) model
  • Scleroderma model
  • Gouty arthritis model
  • Carrageenan-Induced Air Pouch Synovitis Model
  • Carrageenan-Induced Paw Edema Model
  • Experimental Autoimmune Myasthenia Gravis (EAMG) Model
  • Graft-versus-host Disease (GvHD) Model

We provide highly customizable services

  • Innovative approach to projects
  • Extensive in vitro analysis including PCR, histology, and IHC
  • Timely and effective communication
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Oligonucleotide therapeutics are an emerging drug modality, which consists of modified or unmodified short nucleic acid molecules, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), aptamers, and DNAzymes. Oligonucleotide therapeutics can bind to an RNA target by Watson-Crick base pairing. This binding recruits RNAseH, which induces cleavage and degradation of the target RNA. The mechanism can be used to specifically change the expression of disease-relevant proteins. Thus, oligonucleotides are an attractive drug modality that has gained increasing interest in the past years.

Oligonucleotide therapeutics are made from nucleotides containing genetic code, so these therapeutics are very specific and targeted. In some cases, oligonucleotide therapeutics may be customized at an individual level. Creative Bioarray supports the development of oligonucleotide therapeutics. We have extensive experience in oligo in vitro screening using various disease relevant models.

In Vitro Oligo Efficacy Screening

We have a team of scientists dedicated to primary cell culture, custom iPSC generation, genome editing and directed differentiation to help our customers to generate their own "disease-in-a-dish" models. Using a fully optimized high-throughput workflow, Creative Bioarray tests hundreds to thousands of oligonucleotides simultaneously in vitro. This module results in the selection of oligonucleotides that induce knockdown of the target RNA in a dose-responsive manner.

Analyzing Drug Mode of Action

Insight in pathways affected by oligo administration, allows rational selection of combination therapies. Via gene expression profiling and differential gene and pathway analysis in relevant cell lines treated with candidate oligonucleotides, Creative Bioarray provides a list of genes and pathways regulated directly or indirectly by the candidate oligonucleotides.

Bioanalytical Assays

Oligo requires robust and sensitive bioanalytical assays for their quantitation in increasingly complex biological matrices, such as liver, eye, or brain tissues. The bioanalytical assay needs to ensure that there is no interference at low concentrations. Hybridization-based assay is an effective and accurate method to quantify parental oligonucleotides in circulation, and in targeted tissues.

Oligo Safety Assessment

Oligonucleotide therapeutics can also bind to unintended mRNA sequences owing to sequence homology. For this reason, knowing potential side effects and off-target-related toxicity allows you to further prioritize candidate oligonucleotides. Via in silico assessment and experimental validation of putative off-target transcripts in preclinical model systems, Creative Bioarray maps oligo off-target effects of candidate oligonucleotides and generates a list of validated off-target genes for each candidate oligonucleotide.

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Since the late 1980s, antibodies have been used as therapies to treat serious diseases, and demand is soaring to new heights today. However, developing such antibody drugs is by no means easy. The basic requirement is that the antibody binds to its target molecule in an optimal way. At the same time, an antibody drug must fulfil a series of additional criteria. For example, it should not trigger an immune response in the body, it should be efficient to produce using biotechnology, and it should remain stable over a long period of time.

Conventional antibody drug discovery is labor-intensive and slow. Pharmaceutical companies select drug candidates from only a small set of antibodies present in the natural immune system, and have limited information on which candidates are the most promising. In addition, identification and selection of drug targets remain an arduous process because the conventional methods of studying the immune system are not comprehensive.

As a leading contract research organization, Creative Bioarray has extensive experience in the development of optimized therapeutic antibodies. Our unique service portfolio allows us to guide you through your antibody drug discovery journey from target selection to clinical candidate. We work closely with our customers to integrate effective screening strategies, including ELISA, ligand-receptor binding assays, and cell-based assays to identify high-affinity antibodies, blocking antibodies for both protein interactions and biological functions, or agonistic antibodies.

In Vitro Functional Assays

  • Immune checkpoint assay
  • ADCC/CDC/ADCP assay
  • Proliferation, growth inhibition & apoptosis assay
  • Neutralization assay
  • MLR & cytokine release assay
  • Phagocytosis, internalization & endocytosis assay

In Vivo Efficacy, Exploratory PK & Toxicity Studies

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Reproductive toxicology is one of the most complicated areas of toxicology research due to the involvement of multiple organs and tissues, different modes of toxicant action and dependence on the endocrine system. In particular, endocrine disrupters represent a significant challenge for experimental toxicology because of their complex effects on signal networks and programming. A variety of in vivo and in vitro developmental and reproductive toxicology (DART) tests are used to predict the safety of new compounds during drug development, and the results provide the basis for internal decision-making.

At Creative Bioarray, our DART capabilities include pharmaceuticals, biologics, vaccines, gene-therapy products, chemicals, and consumer products. Services cover the whole scope of developmental and reproductive toxicology from embryo fetal, postnatal and juvenile stages to the second generation, testing for the potential effects on fertility.

Male and/or Female Fertility

  • Fertility and early embryonic development to implantation
  • Rat dosed via the clinical route
  • Three doses and a control
  • Dose males 4 weeks prior to mating, females 2 weeks
  • Assess maternal toxicity, development and maturation of gametes, estrous cycles, mating, fertility, and effect on implantation

Embryo Fetal Development

  • Rat and rabbit dosed via the clinical route
  • Three doses and a control
  • Dose during organogenesis (gestation days 6-18)
  • Assess ovarian CLs, implantation sites, resorption, dead fetuses, gross fetal malformations and development variations

Prenatal and Postnatal Development

  • Female rat dosed via the clinical route
  • Three doses and a control
  • Dose from gestation day 6 to lactation day 20
  • Assess maternal toxicity, pregnancy duration, parturition, lactation, implantation, embryo/fetal changes, stillbirths, growth development, behavior and reproductive changes

One-Generation Reproduction

  • Rat of parental generation (F0) dosed via the clinical route
  • Three doses and a control
  • Dose males 10 weeks prior to mating, females 2 weeks
  • Dose both sexes during mating
  • Dose females during pregnancy and for the duration of the nursing period
  • Assess behavioral changes, food consumption, weight, the number and sex of pups, stillbirths, live births, gross anomalies, pathological changes of reproductive organs

Two-Generation Reproduction

  • Rat of first generation (F1) dosed via the clinical route
  • Three doses and a control
  • Dose both sexes 10 weeks prior to mating
  • Dose both sexes 2 weeks during mating
  • Dose females throughout pregnancy and up to the weaning of the F2 offspring
  • Assess sperm parameters, physical development of the F2 offspring, the age of vaginal opening and preputial separation of F1 weanlings, gross abnormalities, pathological changes of reproductive organs
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It is vital for researchers occupied in drug discovery to evaluate parameters of DDIs for the development of safe and effective drug candidates. Creative Bioarray offers TDI assays, including IC50 shift and Kinact/KI assay. We deliver accurate data and detailed experimental protocols to meet your needs.

CYP450 TDI Assay Introduction

  • Why CYP450 TDI Assay?
    • It is widely accepted that the current therapy of multi-drugs inescapably increases the likelihood of drug-drug interactions (DDI). Serious DDIs are a significant risk for new molecular entities (NCE).
    • A large proportion of adverse drug reactions in the clinic can be attributed to drug-drug interactions. Most cited pharmacokinetic DDIs have involved cytochrome P450s (CYPs), responsible for metabolizing 80% of drugs.
    • The forms of CYP inhibition can be roughly divided into two categories. One of them is the inhibition of CYP activity mediated by the drug itself (direct inhibition, DI). Another form is the inhibition mediated by the metabolites derived from the drug (time-dependent inhibition, TDI). In most cases, the inhibition caused by the time-dependent inhibition is irreversible.
    • The consequences of irreversible inhibition are considered to be more severe than reversible inhibition. IC50 shift assay is possible to distinguish between reversible and irreversible inhibition. The kinact and KI values determined can be used to predict the risk of drug-drug interactions.
  • The relationship between IC50 shift and kinact/ KI

CYP450 time-dependent inhibition IC50 shift assay can identify reversible and time-dependent inhibitors. IC50 values often quantify the potential of enzyme-inhibiting drugs. The IC50 change test is currently the standard method used for the preliminary evaluation of TDI.

However, with IC50 shift assay, problems can arise when dealing with irreversible or mechanism-based inhibitors (MBI). The IC50 value of MBI is time-dependent and can cause serious issues when ranking the inhibitory potential of different compounds. Therefore, most studies and ranking schemes associated with MBI depend on the inhibition constant (KI) and enzyme inactivation rate (kinact) instead of the IC50 value.

The kinact/KI assay determines the Kinetic constant of time-dependent inhibition. kinact is the maximum rate of enzyme inactivation at the saturation concentration of the inhibitor, while KI is the concentration of the inhibitor, which gives half of the maximum rate of inactivation. The experimental conditions are determined based on previously performed assays, such as P450 reversible inhibition and time-dependent inhibition: single point or IC50 shift.

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Cryogenic Transmission Electron Microscopy (CryoTEM), commonly known as cryoTEM, is a form of cryogenic electron microscopy, more specifically a type of transmission electron microscopy (TEM) where the sample is studied at cryogenic temperatures (generally liquid-nitrogen temperatures). CryoTEM is gaining popularity in structural biology. The utility of cryoTEM stems from the fact that it allows the observation of specimens that have not been stained or fixed in any way, showing them in their native environment.

In recent years, cryoTEM has evolved into an essential tool for the characterization of colloidal drug delivery systems. The application of this technique is not only confined to size analysis, but also the shape and internal structure of nanoparticulate carrier systems as well as the overall colloidal composition of corresponding dispersions. For example, cryoTEM can provide the data of the ratio of filled and empty capsids, which is a critical quality attribute requirement for any AAV vector manufacturing process. Cryo-TEM involves rapid freezing of AAV suspensions on a perforated sample carrier and visualizing the sample using a cryogenic transmission electron microscope (cryo-TEM), which shows the projections of AAV particles. In other words, the inside of AAVs can be seen. This enables us to determine whether an AAV particle is genome-filled or empty (Figure 1). Genome-filled capsids are characterized by being dark throughout. Empty capsids have dark boundaries at particle edges but are light in the center. Other sample properties like particle uniformity, integrity and clumping are also readily discerned.

The following useful information of the viral vectors can be monitored using cryo-TEM:
The ratio of filled and empty AAV capsids
The internal density of adenoviral vectors
Lentiviral particles exhibiting a visible core
Liposome-like particles


Others depending on the phase of development of sample production
Features of Creative Bioarray's Cryogenic Transmission Electron Microscopy (cryoTEM) Service:
Accurate - When the analysis is finished, we provide you with the TEM images and a detailed report
Value - We focus on the quality of our service and all supported by competitive pricing
Efficiency - We are able to provide the fastest turnaround time of any supplier in the industry