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 (ASC) proprietary TARGATT™ technology, enables fast and site-specific, stable integration of large DNA fragments into an intergenic, transcriptionally active safe harbor locus with very high efficiency. The TARGATT™ gene editing platform is versatile and can generate large fragment knock-in cell line and animal 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.

The TARGATT™ system has been integrated into the TARGATT™ Master iPSC Line. The TARGATT™ Master iPSC Line was engineered from our well-characterized control human iPSC line, ASE-9211 (a NIST iPSC). The master cell line carries an “attP” integrase recognition landing pad in the H11 safe harbor locus. When used in conjunction with an “attB” containing donor plasmid and integrase expression, this master cell line enables site-specific integration of a transgene (up to 22kb) with very high efficiency.

In addition, the TARGATT™ site-specific knockin technology to engineer two additional TARGATT™ Master Cell Lines. The TARGATT™ Master CHO and HEK293 Cell Lines enable single-copy insertion at a safe-harbor locus (H11, ASC2). High integration efficiencies and medium to high levels of protein expression have been observed. These cell lines have the capacity to generate libraries for antibody screening. ASC can produce the library that best fits your project needs, or you can build your own library with the TARGATT™ CHO-K1 Kit (H11) or TARGATT™ HEK293 Kit (H11) for antibody library screening.

ASC is in the process of getting GLP and GMP certified and complied with. We now offer a wide range of GMP clinical-grade induced pluripotent stem cell (iPSC) related services. Applied StemCell’s GMP Grade iPSC line (Cord Blood CD34+, Male) can be engineered to express almost any gene of interest using TARGATT^TM, but ASC can also conduct gene-editing services with the iPSC lines provided by customers. GMP grade knockin cell line generation service using the TARGATT™ Master iPSC Line is also available for single-copy gene insertion at a safe harbor locus.

*If you would like to work with your favorite cell line, ASC can engineer the target system into the cell line of your choice!

TARGATT™ Cell Line Advantages:

• Single copy knockin: 1 cell, 1 docking site, 1 inserted transgene
• Site-specific knockin into a high expression, safe harbor locus (H11, ASC2)
• High efficiency integration (HEK293: >40% without, >90% with drug selection; CHO: ~18% without, >90% with drug selection)
• Large cell library construction in HEK293/ CHO cells
• Cost-effective: no virus packaging time and resources
• BSL1 compatible

Applied StemCell has also used its TAGRATT™ technology to generate several TARGAT™ mouse and rat models. Custom services for TARGATT site-specific knockin mouse and rat model generation are available. As a long-standing leader in custom mouse model engineering, ASC also offers 2,000+ “off-shelf” proprietary, genetically engineered mouse models (GEMM) that are research-ready and can be directly used in gene function, drug screening, and human disease research. Applications for TARGATT™ models:  Transgene overexpression models, humanized gene knockin, reporter gene knock-in, conditional knock-in, inducible expression, and Cre-driver lines.

To learn more about TARGATT^TM and how you can incorporate the technology into your research, contact us today!

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 > 12 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:

• Preclinical proof-of-concept cell line and animal models
• IND-enabling preclinical assay development, validation, and testing: potency, safety/toxicity, efficacy
• Assays include dose ranging, biodistribution and efficacy studies in cell line and animal models for your drug discovery and screening applications
• Consultation for cell and viral vectors manufacturing, analytical methods for drug release (assay development, validation, testing).

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

Applied StemCell (ASC) is in the process of getting GLP and GMP certified and complied with. With its core technologies, CRISPR, TARGATT^TM, and iPSC, ASC can produce almost any gene modification including therapeutic gene/reporter gene insertion, point mutation correction, small nucleotide addition, replacement, and deletion.

ASC can now offer a wide range of GMP clinical-grade induced pluripotent stem cell (iPSC) related services. Applied StemCell’s GMP Grade iPSC line (Cord Blood CD34+, Male) can be engineered to express almost any gene of interest (CRISPR; TARGATT^TM), but ASC can also conduct gene-editing services with the iPSC lines provided by customers. GMP grade knockin cell line generation service using the TARGATT™ Master iPSC Line is also available for single-copy gene insertion at a safe harbor locus.

Along with gene-editing services, ASC offers comprehensive iPSC differentiation service to committed somatic lineages. ASC can work with its GMP iPSC lines or researchers can send in their healthy, diseased, or gene-edited iPSC lines and Applied StemCell will produce the iPSC differentiated cells in its GMP facility.

ASC is working towards developing a comprehensive inventory of GMP clinical-grade iPSC-related products and is currently building a TARGATT^TM Universal Modifiable iPSC platform for therapeutic cell production.

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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 HEK293, CHO cells, stem cells and immortalized cell lines).

Applications:

• Knock-in models: transgene overexpression, reporter gene
• Conditional/ inducible expression models
• Cre-driver mouse lines
• Antibody discovery & screening
• Bioproduction

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.

ASC is a leading provider of genetically engineered mouse models for biomedical research and preclinical drug discovery. With 11+ years of expertise in mouse model engineering and >500 engineered mouse models under our belt, we can engineer advanced, physiologically relevant mouse models with a wide range of precision genetic modifications specific to your projects’ needs.

• Gene knockout, point mutation (SNP), small fragment knock-in, large transgene knock-in (locus-specific and safe harbor locus)
• F1 breeding for germline transmission
• Very efficient and cost-effective protocols

We also offer a repository of off-shelf mouse models that can be directly used for studies on gene function, drug screening, and human diseases, thus effectively shortening your overall experimental cycle.

As an ISO company Applied StemCell can offer you:

• FREE design consultation with our experts
• We can help you develop a gene-editing strategy
• Access to our well characterized control lines
• Full characterization services
• Further differentiation capabilities

Summer Sale! Custom Knockout Mouse Model Generation $10K USD

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Applied StemCell, a long-standing leader in custom mouse model engineering, also offers 2,000+ “off-shelf” proprietary, genetically engineered mouse models (GEMM) that are research-ready and can be directly used in gene function, drug screening, and human disease research.

• Humanized immune checkpoint models with single, double or triple-target modifications in PD1, PD-L1, CTLA4 and other genes.
• Cytokine receptor-related models with fluorescent tags for live-imaging studies.
• Immunodeficient models for immune system and cancer studies.
• Human disease models with knockout, knock-in, conditional knockout mutations.
• Cre recombinase, reporter genes, and Cas9-expressing models and more.
• >30 fluorescent-labeled tumor cell lines for use in in vitro experiments and tumor studies.

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
• 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)

Based on our world-class animal model genetic engineering technologies, Applied StemCell offers a comprehensive suite of downstream assays in mouse and rat models to validate your animal models and for drug screening. 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
• Antibody efficacy testing studies for immunotherapy for cancer and autoimmune disorders

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.

Mammalian Cell-based Protein/ Antibody Discovery & Screening! The TARGATT™ HEK293 Master Cell Line provides an efficient way to generate site-specific, stable, knockin cell lines (even large transgenes) and build large mammalian cell libraries:

• High knockin efficiency: with enrichment (up to 90%) or without (up to 40%)
• Site-specific: H11 locus; active, genomic hotspot
• Single copy integration
• Uniform, high level gene expression
• Unidirectional integration
• Overcomes challenges posed by random integration

The TARGATT™ HEK293 Master Cell Line is ideal for drug screening, toxicity studies, CNS disease or cell modeling, and regenerative medicine studies.

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 two lineages to enable site-specific, single-copy insertion of large transgenes into a preselected safe harbor locus in the CHO cell genome, for high expression levels of your gene of interest. This site-specific TARGATT™ technology overcomes challenges posed by traditional insertion methods, and results in high integration efficiency (>90%), stable knock-in cell lines, uniform gene 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.

Primary cells are isolated from tissues, including blood and bone marrow. The isolated human primary cells have the capacity to function similarly to cells in vivo under the right conditions, and they can be incorporated into various areas of research as model systems. Primary cells can be used for drug discovery, toxicity testing, gene therapy, cancer research, and more.

In order to address the needs of the research community, Applied StemCell (ASC) now offers high-quality fresh and frozen human primary cells, including peripheral blood cells, cord blood cells, and bone marrow cells. ASC also provides hematopoietic stem cells, progenitor cells, and immune cells. For fresh cells, we offer on-demand, customized sample collection and processing services. All donors are IRB-approved and have been tested for Syphilis, Hepatitis B (HBV), Hepatitis C (HCV), HTLV-I/II, HIV-1, and HIV-2. Same-day delivery is available for Bay Area customers. Overnight delivery and international shipping are available for all other customers. Contact us today to learn more.

Applied StemCell (ASC) now offers human hematologic tissue products, including human healthy whole/peripheral blood and cord blood samples. Plasma, Leukopak, and Off-the-clot serum products are available. ASC offers on-site procurement and processing. Our samples are collected from IRB-approved donors who have tested negative for Syphilis, Hepatitis B (HBV), Hepatitis C (HCV), HTLV-I/II, HIV-1, and HIV-2. Contact ASC today to learn more about customized sample collection and requesting a specific donor.

Non-human primate (NHP) cells and hematologic products are now available. Our non-human primate samples are collected from healthy Cynomolgus Macaques or Resus Macaques that are housed in the United States. All of our products come from NHPs that have tested negative for SIV, STLV, SRV, and Herpes B. These high-quality NHP products can be used in disease modeling, toxicity testing, or other areas of research. Applied StemCell provides full customer support from start to finish. You can schedule a consultation today to discuss specific project requirements with one of our experts. You can request an NHP donor of a specific gender or age, and you can reserve the Cynomologus or Rhesus monkey for the entire duration of your project. Contact us today to learn more.

Applied StemCell (ASC) works closely with clinicians to obtain disease samples from patients who have been recently diagnosed or have not received treatment. ASC provides a diverse selection of human fresh and frozen diseased products that can be used for disease modeling, drug development, and other areas of research. Call us today to place your order. We will have the sample ready and, in your hands, the same day of collection when you order one week in advance. ASC offers same-day delivery to Bay Area customers, and overnight and international shipping is available to all customers. The availability of the diseased products is dependent on the prevalence of the disease. If you would like more information, contact us today!

Applied StemCell (ASC) now offers high purity cytokines and growth factors produced by HEK293T cells. We use novel technology to provide customers with high-purity human cytokines that have not been tagged during production. Additionally, our extensive purification methods allow us to generate human cytokines that exhibit super-low levels of endotoxins. ASC’s high purity and high activity cytokines allow you to avoid the higher levels of endotoxin contamination of cytokines from bacteria and other systems. Contact ASC today to speak with one of our experts to learn more about our active human-specific cytokines and which product best fits your project needs.