Research

Accelerate your research and discoveries by leveraging our extensive expertise in stem cell technology! We can provide physiologically relevant in vitro models derived from Pluripotent Stem Cells (PSC) for more predictive models of human disease and biology. ASC offers a comprehensive custom service platform for every aspect of stem cell-based research: iPSC generation/ ESC derivation, CRISPR/Cas9 genome editing and cell line model generation; differentiation to somatic lineage of choice, downstream assays to validate your cell line and for drug discovery and screening.

Cell-based in vitro assays for drug toxicity are becoming crucial tools to screen new drug candidates because they are inexpensive, efficient, and ethically compatible preliminary screening alternatives to the more expensive animal testing models.

Applied StemCell offers a one-stop shopping solution for neurological compound screening. Starting with the engineering of iPSCs from healthy and diseased patient samples; developing disease models via gene editing for drug target discovery and efficacy testing; differentiation into cell lineage(s); cell line model characterization; and ending with a comprehensive panel of cell-based tests for drug efficacy, neurotoxicity, and target discovery that are regulatory compliant.

Save Your Time, Money & Effort! Leverage our extensive expertise in CRISPR/Cas9 genome editing technologies to generate genetically modified mouse, rat, cancer and stem cell lines, with a variety of modifications in a targeted gene of interest. As one of the earliest licensees of CRISPR/Cas9 technology, we have genetically engineered > 1800 unique cell line and animal models for disease modeling, functional genomics, target identification, antibody validation, and validation for drug discovery and screening, and more. We offer affordable, comprehensive custom service with a fast turnaround time to meet the exact requirement of your projects. You can also combine it with our downstream custom assay services for a seamless project workflow.

Applied StemCell’s proprietary TARGATT™ technology, enables site-specific, stable integration of large DNA fragments into a safe harbour locus more efficiently and faster, with guaranteed transgene expression. The TARGATT™ gene-editing platform is versatile and can generate large fragment knock-in animal or cell line models. This technology circumvents problems associated with random integration such as position effect, and gene silencing or instability due to integration of multiple copies of the transgene. Applications for TARGATT™ models: Transgene overexpression models, reporter gene knock-in, conditional knock-in, inducible expression, Cre-driver lines and humanized animal models.

The traditional CHO antibody production and animal bioproduction methods are inefficient because they require random gene insertion and forced amplification of transgenes. Applied StemCell has addressed these problems by utilizing our expertise in cell line and animal model engineering with our proprietary TARGATT™ technology to develop two bioproduction methods: TARGATT™ CHO Master Cell Lines and Transgenic TARGATT™ Rabbits. Both methods offer low-cost, efficiency, consistent protein expression and high protein yield that is easily scalable for large scale bioproduction.

A comprehensive custom Lentiviral-based Stable Cell Line Generation Service for genetically engineering sensitive cells, primary cells, stem cells and terminally differentiated cells. Lentivirus-based stable cell line generation offers a cost-effective and efficient alternative for generating stable cell line models for gene overexpression, inducible gene expression, gene knockout and gene knockdown.

Key Features:

• Modified lentiviruses with broad tropism to target most mammalian species and cell types.
• Non-integrating lentiviruses for CRISPR-lenti gene knockout.
• Choice of selection markers: antibiotic resistance or GFP for FACS.
• Use 3rd generation lentiviral systems for the highest biosafety standards.
• Gene editing confirmed by NGS or RT-PCR.

With >10 years’ experience in molecular biology and genome editing technologies, ASC offers start-to-finish customized services for DNA cloning. vector design and lentivirus/ retrovirus packaging. We can develop the best strategies to tackle your cloning projects and technical problems.

• Lenti-/ retrovirus packaging: Transduction-ready, high titer viruses packaged with your targeting vectors (CRISPR vectors, CAR-T expression vectors)
• CRISPR vector design and cloning for cell line and animal model generation using benchmark strategies and optimized protocols.
• Vector designing or cloning for RNAi/ inducible vectors homologous recombination, Bacterial Artificial Chromosome (BAC) Recombineering, de novo gene synthesis, site-specific mutagenesis, gene tagging, and more.

With >11 years’ experience in genome editing and stem cell technologies, ASC provides ISO:9001 quality, customizable solution-oriented services for advancing preclinical assay development and drug screening for cell and gene therapy pipelines and bioprocessing/ bioproduction:

• In silico, in vitro and in vivo models for target discovery
• Proof-of-concept studies, IND-enabling preclinical assay development including potency assay, dose ranging, biodistribution and efficacy studies in cell line and animal models for your drug discovery and screening applications
• CMC consultation, titration, biologics analysis, and potency assay development, and more…

Customize each part of your project to fit the stage of your research.

Applied StemCell has a comprehensive catalog of products for every aspect of your stem cell research:

• Ready-to-use induced pluripotent stem cell (iPSC).
• iPSC-derived differentiated neural lineage cells.
• For the more hands-on researcher, we offer protocols and kits for iPSC generation to generate your own iPSCs.
• To help you maintain your stem cells, we also offer high quality and thoroughly tested mouse embryonic fibroblasts (MEF) feeder cells, and stem cell-grade “pre-validated“ FBS.

TARGATT™ site-specific knock-in technology enables the integration of transgenes at a preselected locus in the genome, thus overcoming drawbacks of random integration. This technology is adaptable for gene integration in many different species of animals (mice, rats, rabbits, pigs) and cell lines (including CHO cells, stem cells and immortalized cell lines).

Applications:

• Inducible expression models
• Reporter gene insertion models
• Transgene overexpression models
• Humanized animal models
• Cre - driver lines

Isogenic cell lines represent a unique toolset for studying cellular biology, such as the impact of genotype on cellular phenotype, as well as for parallel, high throughput screening to enable the discovery of therapeutic compounds that exhibit genotype-specific toxicity.  An isogenic cell line is a cell line that has been engineered from a parental line through the introduction of a targeted gene mutation. In doing so, the parental cell line inherently becomes a control line to which the engineered line can be referenced. Applied StemCell provides ready-to-use engineered cell lines for cancer and neurodegenerative research as well as reporter lines for quantitative assessments of drug screening experiments.

Stress-free, cost saving solutions for cancer research! ASC offers a series of cell lines and vectors for enabling preclinical cancer research with: a panel of 250+ isogenic cell lines with clinically-relevant cancer mutations (from COSMIC database); and, autobioluminescent cell lines and vectors that uses our revolutionary, optical imaging technology that replaces the traditional method of bioluminescence with a continuous, substrate-free, autobioluminescent signal for efficient screening/monitoring studies and xenograft modeling. Our cell lines and vectors are ideal for:

• Preclinical drug discovery and drug screening; toxicity screening
• Tumorigenesis and treatment studies
• Non-invasive in vivo tumor tracking in small animal models

Applied StemCell provides Human Fibroblast Immortalization Kit for a do-it-yourself alternative to generate your own immortalized cell lines. The Human Fibroblast Immortalization Kit is a mixture of polymers optimized for the infection of lentivirus or retrovirus in most cells, and can increase transduction rate up to 10-fold. Culture with confidence! 

ASC is a leading provider of genetically engineered mouse models for biomedical research and drug discovery. Our custom mouse model generation service includes:

• F1 breeding for germline transmission
• Mouse models engineered in an AAALAC-accredited animal facility
• Two complementary gene editing technologies, CRISPR and TARGATT™ for precise and advanced physiologically relevant mouse models
• New! surgically/ chemically induced mouse models of neurological diseases
• Customized downstream projects for in vivo assessments (automated behavior/ locomotor activity, EEG/ ECG, and pharmacokinetics) as well as in vitro evaluations (electrophysiology, immunohistochemistry, RT-PCR, western blots and more)
• Dedicated project management and timely reports

Genetically engineered rat models are gaining popularity as the preferred biological model for several research areas. ASC can genetically engineer rat models with a physiologically relevant modifications using an expanded technology portfolio with complementary CRISPR/Cas9 and TARGATT™ technologies, as well as, traditional homologous recombination and random transgenic technologies.

• ISO:9001 quality service
• F1 breeding for germline transmission
• AAALAC-accredited animal facility in the USA
• New! surgically/ chemically induced rat models of neurological diseases
• Customized projects for in vivo assessments (automated behavior/ locomotor activity, EEG/ ECG, and pharmacokinetics) as well as in vitro evaluations (electrophysiology, immunohistochemistry & other biochemical assays)

As a long-standing leader in genetically engineered animal models, Applied StemCell also offers a comprehensive custom research solutions platform for downstream assays in mouse and rat models. Our state-of-the-art vivarium is equipped with automated cages & devices for behavioral assessments, sample collection and in vivo measurements (ECG, EEG) of the animals. We have a multidisciplinary team of expert scientists who can design a comprehensive project plan to fit any requirement/stage of your research pipeline and for drug discovery and screening.

• Designing and engineering research animal disease models
• Adoptive transfers/transplantation
• In vivo functional screening assays
• End-of-study in vitro assays

Applied StemCell’s stem cell division has scientists with >75 years of combined experience in stem cell technology. We provide the most comprehensive stem cell related service and product platform for every stage of your stem cell research. Our stem cell service platform makes use the latest and most optimized protocols for efficient and successful projects. Custom stem cell service encompasses stem cell generation, disease modeling, differentiation, characterization to downstream validation of your models and drug screening assays. Our stem cell product catalog includes a variety of ready-to-use, well-characterized iPSC lines, pre-differentiated isogenic panels of neural lineage cells, MEF feeder cells and stem-cell grade FBS among other ISO:9001 quality products.

We know the ins-and-outs of genome editing in cancer cell lines having generated 1300+ cell line models in >200 distinct cell lines. ASC provides expert, high quality enabling tools for cancer research such as precision genome editing to generate physiologically relevant immuno-oncology cell line models and pre-engineered/ isogenic cell lines for early stage drug toxicity screening, generating your own isogenic cell lines and more.

• Multi-approach strategies using complementary CRISPR/Cas9, TARGATT™, and lentiviral technologies
• Engineer a variety of genetic modifications in a wide range of mammalian cell lines
• Customized deliverables and downstream assay/screening services.
• Short turnaround time (as fast as 2 months)

The Ultimate Negative Controls for Genetic Validation of Your Antibodies! Evaluate antibody/ epitope specificity and non-specific binding in gene knockout cell lines. As a leading provider of custom CRISPR Cell Line Genome Editing services, ASC uses highly optimized CRISPR designing strategies and multi-approach protocols to generate frameshift mutations or precisely deleted targeted region(s) of the gene in any cell line of interest, to serve as the ideal negative controls for your antibody validation assays:

• Preliminary expression level confirmation by RT-PCR or Western Blotting
• Gene targeting and knock-out cell line engineering using CRISPR/Cas9
• Optional KO validation by locus-specific sequencing, RT-PCR, or western
• Downstream integration of KO cell lines into FFPE Blocks

UNISELECT™ Mammalian Cell-Based Membrane Proteins Antibody Discovery & Screening! Applied StemCell provides Custom TARGATT™ Master Cell Generation in your cell lines, and ready-to-use TARGATT™ HEK293, and TARGATT™CHO  to build protein libraries using site-specific transgene integration at a preselected safe harbor locus.

This is a fast, unique and efficient platform for biopanning, including bispecific mAbs, antibody discovery, antibody screening, membrane proteins, CAR-T cell screening, and for bioprocessing.

• Single copy integration
• Homogenous expression of protein variants
• Preselected safe harbor locus
• Stable protein expression
• No bacterial backbone insertion
• Inducible expression compatible for membrane proteins (optional)

Cell based assays have become an integral part of preclinical studies to elucidate biological mechanisms, and for screening drugs for efficacy, toxicity or combination analysis for drug synergy or antagonism. The use of live cells in these assays provide a fast and biologically relevant source of information. Applied StemCell offers a fully comprehensive panel of Cell-Based Assays from cell line expansion, cell line model generation, validation, to assays that evaluate cell line function and behavior. We have extensive experience in culturing and handling a wide variety of cell lines including cancer cell lines, immortalized cell lines, stem cells and differentiated cell lines. We will work with you at every stage of your project to fit it to the exact needs of your research.

Make Informed Go-No-Go Decisions Early in Your Drug Development! Process! Applied StemCell (ASC), an ISO-certified service provider offers a flexible assay platform with a wide-range of functional endpoints for early-stage in vitro screening of preclinical drug candidates. We use a comprehensive cell-based test battery from which you can choose assays for efficacy, safety or target discovery that suit your therapeutic pipeline. We will provide the scientific expertise, accurate and efficient screening to help you take informed decisions about your small/ large molecules early in your drug development process to avoid costly drug attrition. Our custom screening service is ideal for CNS, cardiovascular, metabolic, cancer, and immunotherapy drug candidates.

TARGATT™ for Bioproduction of Recombinant Proteins in Chinese Hamster Ovary (CHO) cells. The traditional CHO-cell based protein production is inefficient because it requires random insertion and forced amplification of transgenes.  ASC has “master” TARGATT™ CHO cell lines in 2 lineages: CHO-K1 and CHO-S to enable site-specific, single-copy insertion of large transgenes into a preselected safe harbor locus in the CHO cell genome, for guaranteed gene expression. This site-specific TARGATT™ technology overcomes challenges posed by traditional random insertion methods, and results in high integration efficiency (>90%), stable knock-in cell lines, high levels of transgene expression, and reproducibility of clones. The Master TARGATT™ CHO cell lines are ideal for antibody and recombinant protein expression.

To speed up your research and development; we provide pre-clinical development services (CRO) and support. Our custom services will allow you to focus on the main aspects of your research while we develop the interim paradigms for you.