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Tumor Metabolism and the Microenvironment | EK14


Crispr-engineered nanobodies a potential oncological target against extracellular laminin


Jan 25, 2021 12:00am ‐ Jan 25, 2021 12:00am

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"Crispr-engineered nanobodies a potential oncological target against extracellular laminin" Miss Akanksha Singh CSIR-National Environmental Engineering Research Institute, Nagpur. Abstract: Nanobodies due to low efficiency though effective were when targeted by CRISPR Cas 9 technology conjugated Cas 9 proteins on the surface of nanobody previously tagged with green fluorescent proteins. Laminin is a crucial extracellular proteinaous component in tumoral microenvironment. LN-332 being a multifaceted protein plays an important role in survival and proliferation of cancers thus accelerating the nutrient supply. Nanobodies can engineered specifically against the several types of cancer like colon, oral, prostrate and thyroid. CRISPR- nanostructures can hamper the transcriptome and post-transcriptome of LN-332 component as the Cas 9 proteins loaded on the nanobodies by recognition of rare markers on the surface of LN-332 with the fused fluorescent protein. Nanobodies composed of VHH domain were fused with sg-RNA Cas 9 were exposed to Ln-332 obtained from mice infected with cancer and after 24-48 hours, mice indicated diminished levels of Ln-332 protein. The review juxtaposed therapeutic effect possessed by nanobodies that was accelerated after fusion with Cas 9 proteins might inhibit the activity of LN 332 protein. Keywords: Nanobodies, CRISPR Cas 9, Laminin, LN-332, Cas 9, VHH domain References: 1. Xie, Y.J., Dougan, M., Jailkhani, N., Ingram, J., Fang, T., Kummer, L., Momin, N., Pishesha, N., Rickelt, S., Hynes, R.O. and Ploegh, H., 2019. Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice. Proceedings of the National Academy of Sciences, 116(16), pp.7624-7631. 2. Finicle, B.T., Jayashankar, V. & Edinger, A.L. Nutrient scavenging in cancer. Nat Rev Cancer 18, 619–633 (2018). https://doi.org/10.1038/s41568-018-0048-x 3. Qiu, X., Tan, H., Fu, D., Zhu, Y. and Zhang, J., 2018. Laminin is over expressed in breast cancer and facilitate cancer cell metastasis. Journal of Cancer Research and Therapeutics, 14(12), p.1170. 4. Ye, Y., Zhang, X., Xie, F., Xu, B., Xie, P., Yang, T., Shi, Q., Zhang, C.Y., Zhang, Y., Chen, J. and Jiang, X., 2020. An engineered exosome for delivering sgRNA: Cas9 ribonucleoprotein complex and genome editing in recipient cells. Biomaterials Science, 8(10), pp.2966-2976. 5. Maltseva, D.V. and Rodin, S.A., 2018. Laminins in metastatic cancer. Molecular Biology, 52(3), pp.350-371. 6. Tripathi, M., Nandana, S., Yamashita, H., Ganesan, R., Kirchhofer, D. and Quaranta, V., 2008. Laminin-332 is a substrate for hepsin, a protease associated with prostate cancer progression. Journal of biological chemistry, 283(45), pp.30576-30584.

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