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TARGATT™ Technology and TARGATT™ iPSCs Lines #2


Applied StemCell, TARGATT™

TARGATT™ Technology & TARGATT™ iPSCs

Allogenic/Knock-in Ready for GMP

License-Ready

Consultation Available

Our TARGATT™ iPSC system provides an unlimited starting materials and platform for cell line models as well as therapeutic cell products. TARGATT™ master iPSCs are pluripotent stem cells with a pre-engineered landing pad, attP site, in the H11 safe genomic locus ready for repeated, fast, and efficient gene knock-in by TARGATT™ integrase. The resulting gene edited iPSC can be differentiated to make unlimited, truly off-the-shelf cell products. 

Pain points of current autologous cell therapy approaches include:

  • One product for one patient.
  • Takes months to make. 
  • Patients do not have time.
  • Multiple doses cost millions of $$$.
  • <5% population has access. 

We aim to overcome these bottlenecks through innovative iPSC and TARGATT™ gene editing technologies. 

Why Choose Our TARGATT™ Master iPSC Line
  • Exceptional Efficiency: Our TARGATT™ Master iPSC line offers unparalleled efficiency in site-specific integration of transgenes, achieving higher efficiency compared to other technologies. This precision ensures reliable and consistent results in your research.
  • Site-Specific Integration: The master cell line features an “attP” integrase recognition landing pad in the well-defined, transcriptionally active H11 safe harbor locus. This targeted approach minimizes unintended effects and ensures robust expression of your transgene.
  • Large Cargo Insertion: TARGATT™ allows up to 20kb fragment insertion so multiple genes can be inserted in a single step.
  • Single Copy Integration: With single copy integration, you achieve a more controlled and predictable expression level of your transgene, avoiding the variability and genomic instability associated with multiple copy integrations.
  • Versatile Applications: This master iPSC line is a powerful tool for generating reporter knock-in lines, directed differentiation, and gene overexpression product development. Its precision and efficiency make it ideal for a wide range of applications in stem cell research and cell product development.

Ask an expert about TARGATT™ iPSC master cell lines today
Choose our TARGATT™ Master iPSC line for a superior, reliable solution that advances your research and clinical work with precision and ease.

Ask an expert about TARGATT™ iPSC master cell lines today

  • Publications

    TARGATT™ Master Cell Line

    • Chi, X., Zheng, Q., Jiang, R., Chen-Tsai, R. Y., & Kong, L. J. (2019). A system for site-specific integration of transgenes in mammalian cells. PLOS ONE, 14(7), e0219842.

    Transgenic Mouse Book Chapters

    Description of the technology

    • Zhu, F., Gamboa, M., Farruggio, A. P., Hippenmeyer, S., Tasic, B., Schüle, B., … Calos, M. P. (2014). DICE, an efficient system for iterative genomic editing in human pluripotent stem cells. Nucleic Acids Research, 42(5), e34. http://doi.org/10.1093/nar/gkt1290.
    • Tasic, B., Hippenmeyer, S., Wang, C., Gamboa, M., Zong, H., Chen-Tsai, Y., & Luo, L. (2011). Site-specific integrase-mediated transgenesis in mice via pronuclear injection. Proceedings of the National Academy of Sciences of the United States of America, 108(19), 7902–7907. http://doi.org/10.1073/pnas.1019507108.

    Commentary, comparison with other transgenic methods

    • Rossant, J., Nutter, L. M., & Gertsenstein, M. (2011). Engineering the embryo. Proceedings of the National Academy of Sciences, 108(19), 7659-7660.

    Tet inducible mice generated by TARGATT™

    Advantage of Hipp11 (H11) locus

    Applications for TARGATT™ technology

    • Lindtner, S., Catta-Preta, R., Tian, H., Su-Feher, L., Price, J. D., Dickel, D. E., … & Pennacchio, L. A. (2019). Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons. Cell reports, 28(8), 2048-2063.
    • Wang, T. A., Teo, C. F., Åkerblom, M., Chen, C., Tynan-La Fontaine, M., Greiner, V. J., … & Jan, L. Y. (2019). Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area. Neuron, 103(2), 309-322.
    • Clarke, B. A., Majumder, S., Zhu, H., Lee, Y. T., Kono, M., Li, C., … & Byrnes, C. (2019). The Ormdl genes regulate the sphingolipid synthesis pathway to ensure proper myelination and neurologic function in mice. eLife, 8.
    • Carlson, H. L., & Stadler, H. S. (2019). Development and functional characterization of a lncRNA‐HIT conditional loss of function allele. genesis, e23351.
    • Chande, S., Ho, B., Fetene, J., & Bergwitz, C. (2019). Transgenic mouse model for conditional expression of influenza hemagglutinin-tagged human SLC20A1/PIT1. PloS one, 14(10), e0223052. doi:10.1371/journal.pone.0223052
    • Hu, Q., Ye, Y., Chan, L. C., Li, Y., Liang, K., Lin, A., … & Pan, Y. (2019). Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nature immunology, 1.
    • Matharu, N., Rattanasopha, S., Tamura, S., Maliskova, L., Wang, Y., Bernard, A., … & Ahituv, N. (2018). CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science, eaau0629.
    • Chen-Tsai, R. Y. (2019). Using TARGATT™ Technology to Generate Site-Specific Transgenic Mice. In Microinjection (pp. 71-86). Humana Press, New York, NY
    • Barrett, R. D., Laurent, S., Mallarino, R., Pfeifer, S. P., Xu, C. C., Foll, M., … & Hoekstra, H. E. (2018). The fitness consequences of genetic variation in wild populations of mice. bioRxiv, 383240.
    • Ibrahim, L. A., Huang, J. J., Wang, S. Z., Kim, Y. J., Li, I., & Huizhong, W. (2018). Sparse Labeling and Neural Tracing in Brain Circuits by STARS Strategy: Revealing Morphological Development of Type II Spiral Ganglion Neurons. Cerebral Cortex, 1-14.
    • Kumar, A., Dhar, S., Campanelli, G., Butt, N. A., Schallheim, J. M., Gomez, C. R., & Levenson, A. S. (2018). MTA 1 drives malignant progression and bone metastasis in prostate cancer. Molecular oncology.
    • Jang, Y., Broun, A., Wang, C., Park, Y. K., Zhuang, L., Lee, J. E., … & Ge, K. (2018). H3. 3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development. Nucleic acids research. https://doi.org/10.1093/nar/gky982
    • Tang, Y., Kwon, H., Neel, B. A., Kasher-Meron, M., Pessin, J., Yamada, E., & Pessin, J. E. (2018). The fructose-2, 6-bisphosphatase TIGAR suppresses NF-κB signaling by directly inhibiting the linear ubiquitin assembly complex LUBAC. Journal of Biological Chemistry, jbc-RA118.
    • Chen, M., Geoffroy, C. G., Meves, J. M., Narang, A., Li, Y., Nguyen, M. T., … & Elzière, L. (2018). Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS. Cell Reports, 22(13), 3587-3597
    • Kido, T., Sun, Z., & Lau, Y.-F. C. (2017). Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice. Scientific Reports, 7, 4113. http://doi.org/10.1038/s41598-017-04117-6.
    • Nouri, N., & Awatramani, R. (2017). A novel floor plate boundary defined by adjacent En1 and Dbx1 microdomains distinguishes midbrain dopamine and hypothalamic neurons. Development, 144(5), 916-927.
    • Li, K., Wang, F., Cao, W. B., Lv, X. X., Hua, F., Cui, B., … & Yu, J. M. (2017). TRIB3 Promotes APL Progression through Stabilization of the Oncoprotein PML-RARα and Inhibition of p53-Mediated Senescence. Cancer Cell, 31(5), 697-710.
    • Jiang, T., Kindt, K., & Wu, D. K. (2017). Transcription factor Emx2 controls stereociliary bundle orientation of sensory hair cells. eLife, 6, e23661.
    • Booze, M. L., Hansen, J. M., & Vitiello, P. F. (2016). A Novel Mouse Model for the Identification of Thioredoxin-1 Protein Interactions. Free Radical Biology & Medicine, 99, 533–543. http://doi.org/10.1016/j.freeradbiomed.2016.09.013.
    • Feng, D., Dai, S., Liu, F., Ohtake, Y., Zhou, Z., Wang, H., … & Hayat, U. (2016). Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration. The Journal of clinical investigation, 126(6), 2321-2333.
    • Sun, N., Yun, J., Liu, J., Malide, D., Liu, C., Rovira, I. I., … Finkel, T. (2015). Measuring in vivo mitophagy. Molecular Cell, 60(4), 685–696. http://doi.org/10.1016/j.molcel.2015.10.009.
    • Devine, W. P., Wythe, J. D., George, M., Koshiba-Takeuchi, K., & Bruneau, B. G. (2014). Early patterning and specification of cardiac progenitors in gastrulating mesoderm. eLife, 3, e03848. http://doi.org/10.7554/eLife.03848.
    • Fogg, P. C. M., Colloms, S., Rosser, S., Stark, M., & Smith, M. C. M. (2014). New Applications for Phage Integrases. Journal of Molecular Biology, 426(15), 2703–2716. http://doi.org/10.1016/j.jmb.2014.05.014.
    • Chen-Tsai, R. Y., Jiang, R., Zhuang, L., Wu, J., Li, L., & Wu, J. (2014). Genome editing and animal models. Chinese science bulletin, 59(1), 1-6.
    • Park, K.-E., Park, C.-H., Powell, A., Martin, J., Donovan, D. M., & Telugu, B. P. (2016). Targeted Gene Knockin in Porcine Somatic Cells Using CRISPR/Cas Ribonucleoproteins. International Journal of Molecular Sciences, 17(6), 810. http://doi.org/10.3390/ijms17060810.
    • Guenther, C. A., Tasic, B., Luo, L., Bedell, M. A., & Kingsley, D. M. (2014). A molecular basis for classic blond hair color in Europeans. Nature Genetics, 46(7), 748–752. http://doi.org/10.1038/ng.2991.
    • Villamizar, C. A. (2014). Characterization of the vascular pathology in the acta2 r258c mouse model and cerebrovascular characterization of the acta2 null mouse. UT GSBS Dissertations and These (Open Access). Paper 508 (2014)

MTA Agreement

Material Transfer Agreement

IMPORTANT! PLEASE READ CAREFULLY BEFORE SUBMITTING AN ORDER. THIS IS A CONTRACT.

This Material Transfer Agreement (“MTA”) is between you (“Purchaser”) and the Applied StemCell, Inc. a California company, having its principal place of business at 521 Cottonwood Drive Suite 111, Milpitas, CA 95035 USA (“ASC”). Purchaser must have an approved, current ASC account to place an order. This MTA is effective for a period of five (5) years as of the last date of execution by the parties and governs the purchase and use of all ASC Materials under the terms and conditions set forth below.

TERMS AND CONDITIONS

Definitions

“ASC Material(s)” means materials acquired from ASC as documented on an ASC Sales Order, such as iPS Cell lines.

"ASC Sales Order" means an order submitted for ASC Materials in a form and format as determined by ASC from time to time. "Biological Material(s)" means ASC Materials, Progeny, Unmodified Derivatives and Modifications, either individually or jointly. "Commercial Use" means the sale, license, lease, export, transfer or other distribution of the Biological Materials to a person or entity not party to this MTA for financial gain or other commercial purposes and/or the use of the Biological Material: (a) to provide a service to a person or entity not party to this MTA for financial gain; (b) to produce or manufacture products for general sale or products for use in the manufacture of products ultimately intended for general sale (c) in connection with ADME (Absorption, Distribution, Metabolism and Excretion) testing; (d) in connection with drug potency or toxicity testing (e) in connection with proficiency testing service(s), including but not limited to, providing the service of determining laboratory performance by means of comparing and evaluating calibrations or tests on the same or similar items or materials in accordance with predetermined conditions; or (f) for research conducted under an agreement wherein a for-profit entity receives a right whether actual or contingent to the results of the research. Commercial Use specifically does not include Industry Sponsored Academic Research.

“Contributor(s)” means an organization(s) and/or individual(s) providing original material to ASC for deposit.

"Industry Sponsored Academic Research" means research sponsored by a for-profit organization carried out at a non-profit organization and by the non-profit organization’s employees. "Investigator" means the Purchaser’s principal scientist or researcher using the Biological Material(s). "Modification(s)" mean substances created by Purchaser which contain and/or incorporate a significant or substantial portion of ASC Material. "Progeny" means an unmodified descendant from the ASC Materials, such as virus from virus, cell from cell, or organism from organism. "Purchaser(s)" means the organization purchasing and receiving ASC Material pursuant to this MTA. "Unmodified Derivative(s)" mean substances created by Purchaser that constitute an unmodified functional sub-unit or product not changed in form or character and expressed by the ASC Material provided by ASC. Unmodified Derivatives include, but are not limited to, subclones of unmodified cell lines, purified or fractionated subsets of materials provided by ASC, proteins expressed by DNA/RNA supplied by ASC, or monoclonal antibodies secreted by a hybridoma cell line.

Scope of Use

Subject to the terms of this MTA, Purchaser’s Investigator may make and use the Biological Materials provided to Purchaser by ASC for research purposes only in Purchaser’s Investigator’s laboratory only. The Biological Materials are not intended for use in humans. Purchaser agrees that Biological Materials designated as biosafety level 2 or 3 constitute known pathogens and that other Biological Materials not so designated may be pathogenic under certain conditions. Purchaser assumes all risk and responsibility in connection with the receipt, handling, storage, disposal, transfer and Purchaser’s use of the Biological Materials including without limitation taking all appropriate safety and handling precautions to minimize health or environmental risk. Purchaser agrees that any activity undertaken with the Biological Materials will be conducted in compliance with all applicable guidelines, laws and regulations, and that Purchaser will obtain all permits, licenses or other approvals required by any governmental authority in connection with purchaser’s receipt, handling, storage, disposal, transfer and use of the Biological Materials.

Purchaser shall not distribute, sell, lend or otherwise transfer to a person or entity not party to this MTA the Biological Material, as defined above, for any reason, without ASC’s prior written agreement.

Any Commercial Use of the Biological Material is strictly prohibited without ASC’s prior written consent. Purchaser acknowledges and agrees that Purchaser’s use of certain Biological Material may require a license from a person or entity not party to this MTA, or be subject to restrictions that may be imposed by a person or entity not party to this MTA (“Third Party Terms”). To the extent of ASC’s knowledge of the existence of any such applicable rights or restrictions, ASC will take reasonable steps to identify the same, either in ASC’s catalog of ASC Materials and/or through ASC’s customer service representatives, and to the extent they are in the possession of ASC, ASC shall make information regarding such Third Party Terms reasonably available for review by Purchaser upon request. Purchaser expressly acknowledges that if there is a conflict between this MTA and the Third Party Terms, the Third Party Terms shall govern. Use of the Biological Materials may be subject to the intellectual property rights of a person or entity not party to this MTA, the existence of which rights may or may not be identified in the ASC catalog or website, and ASC makes no representation or warranty regarding the existence or the validity of such rights. Purchaser shall have the sole responsibility for obtaining any intellectual property licenses necessitated by its possession and use of the Biological Materials.

The use permitted under this MTA for Industry Sponsored Academic Research extends only to the academic research carried out at the non-profit organization and the non-profit organization’s employees. Any non-profit Purchaser using the Biological Materials in connection with Industry Sponsored Academic Research agrees to notify the industrial sponsor that any use of the Biological Materials by the industry sponsor will require a separate license from ASC and/or its Contributors and that ASC and/or its Contributors are under no obligation hereunder to license any Biological Materials to any such industry sponsor.

Warranty; Warranty Disclaimer

ASC warrants that (a) cells and microorganisms included in the ASC Material shall be viable upon initiation of culture for a period of thirty (30) days after shipment thereof from ASC and (b) any ASC Material other than cells and microorganisms shall meet the specifications on the applicable ASC Material product information sheet, certificate of analysis, and/or catalog description until the expiration date on the applicable ASC Material’s product label (such thirty (30) day period, or period until the expiration date, referred to herein as the “Warranty Period”). Purchaser’s exclusive remedy, and ASC’s sole liability, for breach of the warranties set forth in this paragraph is for ASC to, at ASC’s sole option, either (i) refund the fee paid to ASC for such ASC Material (exclusive of shipping and handling charges), or (ii) replace the ASC Material. The warranties set forth in this paragraph apply only if Purchaser handles and stores the ASC Material as described in the applicable ASC Material product information sheet. To obtain the exclusive remedy, Purchaser must report the lack of viability or non-conformation to specifications to ASC’s Technical Service Department within the applicable Warranty Period. Any expiration date specified on the ASC Material shipment documentation states the expected remaining useful life, but does not constitute a warranty or extend any applicable Warranty Period. Except as expressly provided above, the ASC Material and any technical information and assistance provided by ASC are provided as-is, without warranties of any kind, express or implied, including but not limited to any implied warranties of merchantability, fitness for a particular purpose, typicality, safety, accuracy and/or non-infringement.

Purchaser acknowledges that the ASC Material and any technical information and assistance provided by ASC are developed and provided exclusively for research purposes, and Purchaser agrees to use the same at its sole risk. Purchaser agrees that ASC and its Contributors will not be liable for any loss, claim or demand made by Purchaser, or made against Purchaser by any other party, due to or arising from the use of the ASC Material by Purchaser, except to the extent permitted by law when caused by the gross negligence or willful misconduct of ASC.

Limitation of Liability

In no event shall ASC or its Contributors be liable for any use of the Biological Material by Purchaser, for any loss, claim, damage, or liability, of whatever kind or nature, which may arise from or in connection with this MTA or the use, handling, storage, or disposal of the Biological Material. ASC’s liability to Purchaser for any claim related to or arising from this MTA or the Biological Material, whether in contract, warranty, tort, or otherwise, shall be limited to the amount paid by Purchaser for the Biological Material. In no event shall ASC be liable for any indirect, special, incidental, consequential, or punitive damages, including without limitation, loss of profits or loss of use, even if ASC has been advised of the possibility of such damages. The limitations of liability set forth in this MTA shall survive termination or expiration of this MTA for any reason.