Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante
Obtener reactivos biológicos mediante su producción in home representa una ventaja importante en el estudio de enfermedades con escenarios multicomponentes como lo es el cáncer, dado a que el suministro extranjero representa una inversión desmedida para un laboratorio de ciencias básicas de un país...
- Autores:
-
Zuluaga Ramírez, Maricela
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2025
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- spa
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/47402
- Acceso en línea:
- https://hdl.handle.net/10495/47402
- Palabra clave:
- Proteínas Recombinantes
Recombinant Proteins
Antígeno B7-H1
B7-H1 Antigen
ADN Recombinante
DNA, Recombinant
Neoplasias
Neoplasms
ADN recombinante
Puntos de control inmnológicos
Puntos de control inmnológicos
https://id.nlm.nih.gov/mesh/D011994
https://id.nlm.nih.gov/mesh/D060890
https://id.nlm.nih.gov/mesh/D004274
https://id.nlm.nih.gov/mesh/D009369
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
- Rights
- openAccess
- License
- http://creativecommons.org/licenses/by-nc-sa/4.0/
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Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante |
| title |
Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante |
| spellingShingle |
Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante Proteínas Recombinantes Recombinant Proteins Antígeno B7-H1 B7-H1 Antigen ADN Recombinante DNA, Recombinant Neoplasias Neoplasms ADN recombinante Puntos de control inmnológicos Puntos de control inmnológicos https://id.nlm.nih.gov/mesh/D011994 https://id.nlm.nih.gov/mesh/D060890 https://id.nlm.nih.gov/mesh/D004274 https://id.nlm.nih.gov/mesh/D009369 ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades |
| title_short |
Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante |
| title_full |
Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante |
| title_fullStr |
Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante |
| title_full_unstemmed |
Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante |
| title_sort |
Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinante |
| dc.creator.fl_str_mv |
Zuluaga Ramírez, Maricela |
| dc.contributor.advisor.none.fl_str_mv |
Patiño González, Edwin Bairon |
| dc.contributor.author.none.fl_str_mv |
Zuluaga Ramírez, Maricela |
| dc.contributor.researchgroup.none.fl_str_mv |
Grupo de Bioquímica Estructural de Macromoléculas |
| dc.subject.decs.none.fl_str_mv |
Proteínas Recombinantes Recombinant Proteins Antígeno B7-H1 B7-H1 Antigen ADN Recombinante DNA, Recombinant Neoplasias Neoplasms |
| topic |
Proteínas Recombinantes Recombinant Proteins Antígeno B7-H1 B7-H1 Antigen ADN Recombinante DNA, Recombinant Neoplasias Neoplasms ADN recombinante Puntos de control inmnológicos Puntos de control inmnológicos https://id.nlm.nih.gov/mesh/D011994 https://id.nlm.nih.gov/mesh/D060890 https://id.nlm.nih.gov/mesh/D004274 https://id.nlm.nih.gov/mesh/D009369 ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades |
| dc.subject.proposal.spa.fl_str_mv |
ADN recombinante Puntos de control inmnológicos Puntos de control inmnológicos |
| dc.subject.meshuri.none.fl_str_mv |
https://id.nlm.nih.gov/mesh/D011994 https://id.nlm.nih.gov/mesh/D060890 https://id.nlm.nih.gov/mesh/D004274 https://id.nlm.nih.gov/mesh/D009369 |
| dc.subject.ods.none.fl_str_mv |
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades |
| description |
Obtener reactivos biológicos mediante su producción in home representa una ventaja importante en el estudio de enfermedades con escenarios multicomponentes como lo es el cáncer, dado a que el suministro extranjero representa una inversión desmedida para un laboratorio de ciencias básicas de un país en desarrollo, en términos de costo, cantidad y disponibilidad. Por ello, se realiza la expresión del dominio extracelular (DEC) de la proteína humana PD-L1 (ligando de muerte programada 1) empleando tecnología del ADN recombinante, su purificación usando cromatografía de afinidad y su respectiva caracterización a través de técnicas analíticas y de fácil acceso como el SDS-PAGE y el Western Blot. Obteniendo como resultado la producción de proteína recombinante humana PD-L1-DEC con un rendimiento del 7.8% al obtener 7.8 mg de proteína, con un alto grado de pureza asociada a una única banda bien diferenciada en los geles de poliacrilamida y la verificación de su identidad mediante el reconocimiento de esta por un anticuerpo monoclonal anti-PD-L1 comercial. A través de este proceso metodológicamente viable se obtiene PD-L1 recombinante funcional para su aplicación en experimentos de interés biomédico. |
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2025 |
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2025-09-19T19:23:09Z |
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2025 |
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Trabajo de grado - Pregrado |
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Arafat Hossain, Md. 2024. “A Comprehensive Review of Immune Checkpoint Inhibitors for Cancer Treatment.” International Immunopharmacology 143:113365. doi:10.1016/j.intimp.2024.113365. Begg, G., and D. Speicher. 1999. “Mass Spectrometry Detection and Reduction of Disulfide Adducts between Reducing Agents and Recombinant Proteins with Highly Reactive Cysteines.” Journal of Biomolecular Techniques : JBT 10(1):17–20. Bowden, Gregory A., Angel M. Paredes, and George Georgiou. 1991. “Structure and Morphology of Protein Inclusion Bodies in Escherichia Coli.” Bio/Technology 9(8):725–30. doi:10.1038/nbt0891-725. Cossar, J. D., and C. H. Arrowsmith. 2012. “1.3 Efficient Strategies for Production of Eukaryotic Proteins.” Pp. 4–33 in Comprehensive Biophysics, edited by E. H. Egelman. Amsterdam: Elsevier. Doroshow, Deborah Blythe, Sheena Bhalla, Mary Beth Beasley, Lynette M. Sholl, Keith M. Kerr, Sacha Gnjatic, Ignacio I. Wistuba, David L. Rimm, Ming Sound Tsao, and Fred R. Hirsch. 2021. “PD-L1 as a Biomarker of Response to Immune-Checkpoint Inhibitors.” Nature Reviews Clinical Oncology 18(6):345–62. doi:10.1038/s41571-021-00473-5. Gavini, Kartheek, and Kodeeswaran Parameshwaran. 2025. “Western Blot.” in StatPearls. Treasure Island (FL): StatPearls Publishing. İncir, İbrahim, and Özlem Kaplan. 2024. “Escherichia Coli as a Versatile Cell Factory: Advances and Challenges in Recombinant Protein Production.” Protein Expression and Purification 219:106463. doi:10.1016/j.pep.2024.106463. Kumar, D. 2011. “Protein Refolding/Renaturation.” Pp. 765–84 in Comprehensive Biotechnology. Elsevier. Kumari, Neetu, Mettle Brahma, and Mulaka Maruthi. 2023. “Chapter 6 - Targeting Immune Checkpoints for Cancer Therapy.” Pp. 95–134 in Treatment Landscape of Targeted Therapies in Oncology, edited by P. K. Maurya and V. Saini. Academic Press. Kythreotou, Anthousa, Abdul Siddique, Francesco A. Mauri, Mark Bower, and David J. Pinato. 2018. “Pd-L1.” Journal of Clinical Pathology 71(3):189–94. doi:10.1136/jclinpath-2017-204853. Lin, David Yin-wei, Yoshimasa Tanaka, Masashi Iwasaki, Apostolos G. Gittis, Hua-Poo Su, Bunzo Mikami, Taku Okazaki, Tasuku Honjo, Nagahiro Minato, and David N. Garboczi. 2008. “The PD-1/PD-L1 Complex Resembles the Antigen-Binding Fv Domains of Antibodies and T Cell Receptors.” Proceedings of the National Academy of Sciences 105(8):3011–16. doi:10.1073/pnas.0712278105. LLC, GSL Biotech. n.d. “pET-28a(+) Sequence and Map.” Retrieved July 27, 2025. https://www.snapgene.com/plasmids/pet_and_duet_vectors_(novagen)/pET-28a(%2B). Manns, Joanne M. 2011. “SDS‐Polyacrylamide Gel Electrophoresis (SDS‐PAGE) of Proteins.” Current Protocols in Microbiology 22(1). doi:10.1002/9780471729259.mca03ms22. Mohan, Sudesh B. 1992. “Determination of Purity and Yield.” Pp. 307–23 in Practical Protein Chromatography, edited by A. Kenney and S. Fowell. Totowa, NJ: Humana Press. Patel, Sandip Pravin, and Razelle Kurzrock. 2015. “PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy.” Molecular Cancer Therapeutics 14(4):847–56. doi:10.1158/1535-7163.mct-14-0983. Rosano, Germán L., and Eduardo A. Ceccarelli. 2014. “Recombinant Protein Expression in Escherichia Coli: Advances and Challenges.” Frontiers in Microbiology 5. doi:10.3389/fmicb.2014.00172. Saraswat, Mayank, Luca Musante, Alessandra Ravidá, Brian Shortt, Barry Byrne, and Harry Holthofer. 2013. “Preparative Purification of Recombinant Proteins: Current Status and Future Trends.” BioMed Research International 2013(1):312709. doi:10.1155/2013/312709. Singh, Anupam, Vaibhav Upadhyay, Arun Kumar Upadhyay, Surinder Mohan Singh, and Amulya Kumar Panda. 2015. “Protein Recovery from Inclusion Bodies of Escherichia Coli Using Mild Solubilization Process.” Microbial Cell Factories 14(1):41. doi:10.1186/s12934-015-0222-8. Sun, Chong, Riccardo Mezzadra, and Ton N. Schumacher. 2018. “Regulation and Function of the PD-L1 Checkpoint.” Immunity 48(3):434–52. doi:10.1016/j.immuni.2018.03.014. Swanton, Charles, Elsa Bernard, Chris Abbosh, Fabrice André, Johan Auwerx, Allan Balmain, Dafna Bar-Sagi, René Bernards, Susan Bullman, James DeGregori, Catherine Elliott, Ayelet Erez, Gerard Evan, Mark A. Febbraio, Andrés Hidalgo, Mariam Jamal-Hanjani, Johanna A. Joyce, Matthew Kaiser, Katja Lamia, Jason W. Locasale, Sherene Loi, Ilaria Malanchi, Miriam Merad, Kathryn Musgrave, Ketan J. Patel, Sergio Quezada, Jennifer A. Wargo, Ashani Weeraratna, Eileen White, Frank Winkler, John N. Wood, Karen H. Vousden, and Douglas Hanahan. 2024. “Embracing Cancer Complexity: Hallmarks of Systemic Disease.” Cell 187(7):1589–1616. doi:10.1016/j.cell.2024.02.009. Tegel, Hanna, Samuel Tourle, Jenny Ottosson, and Anja Persson. 2010. “Increased Levels of Recombinant Human Proteins with the Escherichia Coli Strain Rosetta(DE3).” Protein Expression and Purification 69(2):159–67. doi:10.1016/j.pep.2009.08.017. Thomson, Christy A., Melanie Olson, Linda M. Jackson, and John W. Schrader. 2012. “A Simplified Method for the Efficient Refolding and Purification of Recombinant Human GM-CSF.” PLOS ONE 7(11):e49891. doi:10.1371/journal.pone.0049891. Tripathi, Nagesh K. 2016. “Production and Purification of Recombinant Proteins from Escherichia Coli.” ChemBioEng Reviews 3(3):116–33. doi:10.1002/cben.201600002. Tsumoto, Kouhei, Daisuke Ejima, Izumi Kumagai, and Tsutomu Arakawa. 2003. “Practical Considerations in Refolding Proteins from Inclusion Bodies.” Protein Expression and Purification 28(1):1–8. doi:10.1016/s1046-5928(02)00641-1. Vectors. 2013. Pp. 277–80 in Brenner’s Encyclopedia of Genetics. Elsevier. Yarchoan, Mark, Lee A. Albacker, Alexander C. Hopkins, Meagan Montesion, Karthikeyan Murugesan, Teena T. Vithayathil, Neeha Zaidi, Nilofer S. Azad, Daniel A. Laheru, Garrett M. Frampton, and Elizabeth M. Jaffee. 2019. “PD-L1 Expression and Tumor Mutational Burden Are Independent Biomarkers in Most Cancers.” JCI Insight 4(6). doi:10.1172/jci.insight.126908. Zak, Krzysztof M., Radoslaw Kitel, Sara Przetocka, Przemyslaw Golik, Katarzyna Guzik, Bogdan Musielak, Alexander Dömling, Grzegorz Dubin, and Tad A. Holak. 2015. “Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1.” Structure 23(12):2341–48. doi:10.1016/j.str.2015.09.010. |
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Patiño González, Edwin BaironZuluaga Ramírez, MaricelaGrupo de Bioquímica Estructural de Macromoléculas2025-09-19T19:23:09Z2025https://hdl.handle.net/10495/47402Obtener reactivos biológicos mediante su producción in home representa una ventaja importante en el estudio de enfermedades con escenarios multicomponentes como lo es el cáncer, dado a que el suministro extranjero representa una inversión desmedida para un laboratorio de ciencias básicas de un país en desarrollo, en términos de costo, cantidad y disponibilidad. Por ello, se realiza la expresión del dominio extracelular (DEC) de la proteína humana PD-L1 (ligando de muerte programada 1) empleando tecnología del ADN recombinante, su purificación usando cromatografía de afinidad y su respectiva caracterización a través de técnicas analíticas y de fácil acceso como el SDS-PAGE y el Western Blot. Obteniendo como resultado la producción de proteína recombinante humana PD-L1-DEC con un rendimiento del 7.8% al obtener 7.8 mg de proteína, con un alto grado de pureza asociada a una única banda bien diferenciada en los geles de poliacrilamida y la verificación de su identidad mediante el reconocimiento de esta por un anticuerpo monoclonal anti-PD-L1 comercial. A través de este proceso metodológicamente viable se obtiene PD-L1 recombinante funcional para su aplicación en experimentos de interés biomédico.Obtaining biological reagents through in-house production represents a significant advantage in the study of diseases with multicomponent scenarios, such as cancer. This is because foreign supply represents a disproportionate investment for a basic science laboratory in a developing country, in terms of cost, quantity, and availability. Therefore, the expression of the extracellular domain (ECD) of the human PD-L1 protein (Programmed Death Ligand 1) was performed using recombinant DNA technology, its purification using affinity chromatography, and its respective characterization through accessible analytical techniques such as SDS-PAGE and Western Blot. The result was the production of recombinant human PD-L1 ECD protein with a yield of 7.8% (obtaining 7.8 mg of protein), displaying a high degree of purity associated with a single well-differentiated band on polyacrylamide gels. Its functionality was verified through recognition by a commercial anti-PD-L1 monoclonal antibody. Through this methodologically viable process, functional recombinant PD-L1 is obtained for application in biomedical experiments of interest.Fisiología QuímicaPregradoQuímico35 páginasapplication/pdfspaUniversidad de AntioquiaQuímicaMedellín, ColombiaFacultad de Ciencias Exactas y NaturalesCampus Medellín - Ciudad Universitariahttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Producción de la proteína humana PD-L1 mediante tecnología del ADN recombinanteTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/redcol/resource_type/TPTexthttp://purl.org/coar/version/c_b1a7d7d4d402bcceinfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/draftArafat Hossain, Md. 2024. “A Comprehensive Review of Immune Checkpoint Inhibitors for Cancer Treatment.” International Immunopharmacology 143:113365. doi:10.1016/j.intimp.2024.113365.Begg, G., and D. Speicher. 1999. “Mass Spectrometry Detection and Reduction of Disulfide Adducts between Reducing Agents and Recombinant Proteins with Highly Reactive Cysteines.” Journal of Biomolecular Techniques : JBT 10(1):17–20.Bowden, Gregory A., Angel M. Paredes, and George Georgiou. 1991. “Structure and Morphology of Protein Inclusion Bodies in Escherichia Coli.” Bio/Technology 9(8):725–30. doi:10.1038/nbt0891-725.Cossar, J. D., and C. H. Arrowsmith. 2012. “1.3 Efficient Strategies for Production of Eukaryotic Proteins.” Pp. 4–33 in Comprehensive Biophysics, edited by E. H. Egelman. Amsterdam: Elsevier.Doroshow, Deborah Blythe, Sheena Bhalla, Mary Beth Beasley, Lynette M. Sholl, Keith M. Kerr, Sacha Gnjatic, Ignacio I. Wistuba, David L. Rimm, Ming Sound Tsao, and Fred R. Hirsch. 2021. “PD-L1 as a Biomarker of Response to Immune-Checkpoint Inhibitors.” Nature Reviews Clinical Oncology 18(6):345–62. doi:10.1038/s41571-021-00473-5.Gavini, Kartheek, and Kodeeswaran Parameshwaran. 2025. “Western Blot.” in StatPearls. Treasure Island (FL): StatPearls Publishing.İncir, İbrahim, and Özlem Kaplan. 2024. “Escherichia Coli as a Versatile Cell Factory: Advances and Challenges in Recombinant Protein Production.” Protein Expression and Purification 219:106463. doi:10.1016/j.pep.2024.106463.Kumar, D. 2011. “Protein Refolding/Renaturation.” Pp. 765–84 in Comprehensive Biotechnology. Elsevier.Kumari, Neetu, Mettle Brahma, and Mulaka Maruthi. 2023. “Chapter 6 - Targeting Immune Checkpoints for Cancer Therapy.” Pp. 95–134 in Treatment Landscape of Targeted Therapies in Oncology, edited by P. K. Maurya and V. Saini. Academic Press.Kythreotou, Anthousa, Abdul Siddique, Francesco A. Mauri, Mark Bower, and David J. Pinato. 2018. “Pd-L1.” Journal of Clinical Pathology 71(3):189–94. doi:10.1136/jclinpath-2017-204853.Lin, David Yin-wei, Yoshimasa Tanaka, Masashi Iwasaki, Apostolos G. Gittis, Hua-Poo Su, Bunzo Mikami, Taku Okazaki, Tasuku Honjo, Nagahiro Minato, and David N. Garboczi. 2008. “The PD-1/PD-L1 Complex Resembles the Antigen-Binding Fv Domains of Antibodies and T Cell Receptors.” Proceedings of the National Academy of Sciences 105(8):3011–16. doi:10.1073/pnas.0712278105.LLC, GSL Biotech. n.d. “pET-28a(+) Sequence and Map.” Retrieved July 27, 2025. https://www.snapgene.com/plasmids/pet_and_duet_vectors_(novagen)/pET-28a(%2B).Manns, Joanne M. 2011. “SDS‐Polyacrylamide Gel Electrophoresis (SDS‐PAGE) of Proteins.” Current Protocols in Microbiology 22(1). doi:10.1002/9780471729259.mca03ms22.Mohan, Sudesh B. 1992. “Determination of Purity and Yield.” Pp. 307–23 in Practical Protein Chromatography, edited by A. Kenney and S. Fowell. Totowa, NJ: Humana Press.Patel, Sandip Pravin, and Razelle Kurzrock. 2015. “PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy.” Molecular Cancer Therapeutics 14(4):847–56. doi:10.1158/1535-7163.mct-14-0983.Rosano, Germán L., and Eduardo A. Ceccarelli. 2014. “Recombinant Protein Expression in Escherichia Coli: Advances and Challenges.” Frontiers in Microbiology 5. doi:10.3389/fmicb.2014.00172.Saraswat, Mayank, Luca Musante, Alessandra Ravidá, Brian Shortt, Barry Byrne, and Harry Holthofer. 2013. “Preparative Purification of Recombinant Proteins: Current Status and Future Trends.” BioMed Research International 2013(1):312709. doi:10.1155/2013/312709.Singh, Anupam, Vaibhav Upadhyay, Arun Kumar Upadhyay, Surinder Mohan Singh, and Amulya Kumar Panda. 2015. “Protein Recovery from Inclusion Bodies of Escherichia Coli Using Mild Solubilization Process.” Microbial Cell Factories 14(1):41. doi:10.1186/s12934-015-0222-8.Sun, Chong, Riccardo Mezzadra, and Ton N. Schumacher. 2018. “Regulation and Function of the PD-L1 Checkpoint.” Immunity 48(3):434–52. doi:10.1016/j.immuni.2018.03.014.Swanton, Charles, Elsa Bernard, Chris Abbosh, Fabrice André, Johan Auwerx, Allan Balmain, Dafna Bar-Sagi, René Bernards, Susan Bullman, James DeGregori, Catherine Elliott, Ayelet Erez, Gerard Evan, Mark A. Febbraio, Andrés Hidalgo, Mariam Jamal-Hanjani, Johanna A. Joyce, Matthew Kaiser, Katja Lamia, Jason W. Locasale, Sherene Loi, Ilaria Malanchi, Miriam Merad, Kathryn Musgrave, Ketan J. Patel, Sergio Quezada, Jennifer A. Wargo, Ashani Weeraratna, Eileen White, Frank Winkler, John N. Wood, Karen H. Vousden, and Douglas Hanahan. 2024. “Embracing Cancer Complexity: Hallmarks of Systemic Disease.” Cell 187(7):1589–1616. doi:10.1016/j.cell.2024.02.009.Tegel, Hanna, Samuel Tourle, Jenny Ottosson, and Anja Persson. 2010. “Increased Levels of Recombinant Human Proteins with the Escherichia Coli Strain Rosetta(DE3).” Protein Expression and Purification 69(2):159–67. doi:10.1016/j.pep.2009.08.017.Thomson, Christy A., Melanie Olson, Linda M. Jackson, and John W. 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