Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa

Ilustraciones

Autores:
Nova López, Carlos Julio
Tipo de recurso:
Fecha de publicación:
2023
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/85444
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/85444
https://repositorio.unal.edu.co/
Palabra clave:
570 - Biología
580 - Plantas
630 - Agricultura y tecnologías relacionadas
Papa (Solanum tuberosum subsp. andígena var. pastusa suprema)
Cultivo in vitro
ADN recombinante
Proteínas recombinantes
factor de crecimiento epidérmico humano recombinante (rhEGF)
Cultivo in vitro
Solanum tuberosum
Agrobacterium tumefaciens
Recombinant proteins
in vitro culture
Solanum tuberosum
Agrobacterium tumefaciens
Recombinant human epidermal growth factor (rhEGF)
Rights
openAccess
License
Atribución-NoComercial-SinDerivadas 4.0 Internacional
id UNACIONAL2_46c6c9b5cee5b8f5f89c059d6f23390e
oai_identifier_str oai:repositorio.unal.edu.co:unal/85444
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
dc.title.translated.eng.fl_str_mv Advances in the establishment of a platform for the production of recombinant human epidermal growth factor (rhEGF) using in vitro potato cultures
title Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
spellingShingle Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
570 - Biología
580 - Plantas
630 - Agricultura y tecnologías relacionadas
Papa (Solanum tuberosum subsp. andígena var. pastusa suprema)
Cultivo in vitro
ADN recombinante
Proteínas recombinantes
factor de crecimiento epidérmico humano recombinante (rhEGF)
Cultivo in vitro
Solanum tuberosum
Agrobacterium tumefaciens
Recombinant proteins
in vitro culture
Solanum tuberosum
Agrobacterium tumefaciens
Recombinant human epidermal growth factor (rhEGF)
title_short Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
title_full Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
title_fullStr Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
title_full_unstemmed Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
title_sort Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papa
dc.creator.fl_str_mv Nova López, Carlos Julio
dc.contributor.advisor.none.fl_str_mv Arango Isaza, Rafael Eduardo
Torres Bonilla, Javier Mauricio
dc.contributor.author.none.fl_str_mv Nova López, Carlos Julio
dc.contributor.researchgroup.spa.fl_str_mv Biotecnología Vegetal UNALMED-CIB
dc.contributor.orcid.spa.fl_str_mv 0000-0003-3128-4539
dc.contributor.cvlac.spa.fl_str_mv https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0001583298
dc.subject.ddc.spa.fl_str_mv 570 - Biología
580 - Plantas
630 - Agricultura y tecnologías relacionadas
topic 570 - Biología
580 - Plantas
630 - Agricultura y tecnologías relacionadas
Papa (Solanum tuberosum subsp. andígena var. pastusa suprema)
Cultivo in vitro
ADN recombinante
Proteínas recombinantes
factor de crecimiento epidérmico humano recombinante (rhEGF)
Cultivo in vitro
Solanum tuberosum
Agrobacterium tumefaciens
Recombinant proteins
in vitro culture
Solanum tuberosum
Agrobacterium tumefaciens
Recombinant human epidermal growth factor (rhEGF)
dc.subject.agrovoc.none.fl_str_mv Papa (Solanum tuberosum subsp. andígena var. pastusa suprema)
dc.subject.lemb.none.fl_str_mv Cultivo in vitro
ADN recombinante
dc.subject.proposal.spa.fl_str_mv Proteínas recombinantes
factor de crecimiento epidérmico humano recombinante (rhEGF)
Cultivo in vitro
Solanum tuberosum
Agrobacterium tumefaciens
dc.subject.proposal.eng.fl_str_mv Recombinant proteins
in vitro culture
Solanum tuberosum
Agrobacterium tumefaciens
Recombinant human epidermal growth factor (rhEGF)
description Ilustraciones
publishDate 2023
dc.date.issued.none.fl_str_mv 2023-05-02
dc.date.accessioned.none.fl_str_mv 2024-01-25T15:53:34Z
dc.date.available.none.fl_str_mv 2024-01-25T15:53:34Z
dc.type.spa.fl_str_mv Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/85444
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/85444
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.indexed.spa.fl_str_mv LaReferencia
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spelling Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Arango Isaza, Rafael Eduardob7e61322453072ebf7408a0f587e39c1600Torres Bonilla, Javier Mauricio315aa45692339fe7f1e42ff1588fbab0600Nova López, Carlos Julio8541b76b58facc8a2e703641a81fe2e0Biotecnología Vegetal UNALMED-CIB0000-0003-3128-4539https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=00015832982024-01-25T15:53:34Z2024-01-25T15:53:34Z2023-05-02https://repositorio.unal.edu.co/handle/unal/85444Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/IlustracionesLas proteínas recombinantes terapéuticas constituyen la base para el tratamiento de muchas de las enfermedades complejas que aquejan a la humanidad, por lo que se han posicionado como el sector de mayor crecimiento dentro de la industria farmacéutica. Tradicionalmente los cultivos bacterianos, de levaduras y de células de mamífero se han utilizado como plataformas de producción de estos medicamentos, pero en los últimos años los cultivos de plantas y de células vegetales han emergido como una nueva alternativa de expresión, con incluso casos de medicamentos que han alcanzado fases avanzadas de desarrollo o de mercado. El objetivo de este trabajo fue avanzar en el proceso de desarrollo de una plataforma basada en el uso de cultivos in vitro de papa (Solanum tuberosum subsp. andígena var. pastusa suprema) que permita en un futuro la producción heteróloga del factor de crecimiento epidérmico humano (hEGF), una proteína con importantes aplicaciones terapéuticas y cosméticas. Para esto, se presentan aportes en aspectos relacionados con: i) el establecimiento de cultivos de plantas de papa no transformadas, ii) el diseño in silico y la síntesis de casetes genéticos para la expresión del hEGF, iii) la obtención de cepas de Agrobacterium tumefaciens transformadas con los vectores de expresión y iv) la ejecución de ensayos preliminares de transformación genética para la obtención de líneas de plantas transformadas con el gen hEGF. De manera particular, se propone la inducción de la brotación de tubérculos de papa con el uso de GA3 y la incubación de las semillas a 26 0C bajo fotoperiodo natural como estrategia para la obtención del material de partida requerido para el desarrollo de los cultivos no transformados. No se encontraron diferencias significativas en los porcentajes de desinfección de los brotes cuando se usaron hipoclorito de sodio o bicloruro de mercurio como agentes de desinfección, aunque el porcentaje de supervivencia de los explantes se vio favorecido con el uso de hipoclorito. Se diseñaron dos casetes de expresión que, además de contener la secuencia hEGF con el uso codónico optimizado para la expresión en papa, incluyen también secuencias promotoras (CaMV 35S 2x), terminadoras (Pin II) y otros elementos regulatorios (secuencia 5’ UTR, secuencia de señalización, secuencia de retención, colas Hisx6 y sitios de unión a la matriz extracelular) seleccionados estratégicamente con el fin de garantizar elevados niveles de expresión, producción y purificación de la proteína. Los casetes se clonaron en el vector pCAMBIA 2300 y se introdujeron, previa confirmación por secuenciación, en cepas de Agrobacterium tumfaciens EHA 105 y LBA4400, lo que permitió la obtención de colonias transformantes que se confirmaron por PCR y que fueron empleadas en ensayos preliminares de infección de hojas y entrenudos con el fin de evaluar la formación de callo y la eventual regeneración de plantas transformadas. Aunque el porcentaje de formación de callo en los explantes de hoja sometidos a infección fue bajo y aunque se observó una pobre capacidad regenerativa en dos tipos de explante utilizados, los avances obtenidos sirven de insumo para el desarrollo de investigaciones futuras que tengan por objetivo principal el desarrollo de cultivos transgénicos de papa y la evaluación de la producción del rhEGF en esta plataforma vegetal. (texto tomado de la fuente)Therapeutic recombinant proteins are the basis for the treatment of many complex diseases that afflict humanity, making them the fastest-growing sector in the pharmaceutical industry. Bacterial, yeast, and mammalian cell cultures have traditionally been used as production platforms for these medicines, but in recent years, plant and plant cell cultures have emerged as a new expression alternative, with even cases of drugs that have reached advanced stages of development or market. The objective of this work was to advance the development process of a platform based on the use of in vitro potato cultures (Solanum tuberosum subsp. andígena var. pastusa suprema) that will allow for future heterologous production of human epidermal growth factor (hEGF), a protein with important therapeutic and cosmetic applications. Contributions are presented in aspects related to: i) the establishment of non-transformed potato plant cultures, ii) in silico design and genetic cassette synthesis for hEGF expression, iii) the generation of transformed Agrobacterium tumefaciens strains with expression vectors, and iv) preliminary genetic transformation assays to obtain transformed plant lines with the hEGF gene. Particularly, the induction of potato tuber sprouting using GA3 and seed incubation at 26 0C under natural photoperiod is proposed as a strategy to obtain the required starting material for non-transformed culture development. There were no significant differences in disinfection percentages of the shoots when sodium hypochlorite or mercuric bichloride were used as disinfection agents, although the explants' survival rate was favored with the use of hypochlorite. Two expression cassettes were designed that, in addition to containing the hEGF sequence with optimized codon usage for expression in potato, also include promoter (CaMV 35S 2x), terminator (Pin II), and other regulatory elements (5’ UTR sequence, signaling sequence, retention sequence, Hisx6 tails, and extracellular matrix binding sites) strategically selected to guarantee high expression levels, production, and purification of the protein. The cassettes were cloned into the pCAMBIA 2300 vector and introduced, after confirmation by sequencing, into Agrobacterium tumfaciens EHA 105 and LBA4400 strains, allowing the obtaining of transforming colonies confirmed by PCR and used in preliminary infection assays of leaves and internodes to evaluate callus formation and eventual regeneration of transformed plants. Although the percentage of callus formation in infected leaf explants was low, and poor regenerative capacity was observed in two types of explants used, the advances obtained serve as input for future research aimed at developing transgenic potato cultures and evaluating rhEGF production on this plant platformMaestríaMagíster en Ciencias AgrariasÁrea Curricular en Producción Agraria Sostenible121 páginasapplication/pdfspaUniversidad Nacional de ColombiaMedellín - Ciencias Agrarias - Maestría en Ciencias AgrariasFacultad de Ciencias AgrariasMedellín, ColombiaUniversidad Nacional de Colombia - Sede Medellín570 - Biología580 - Plantas630 - Agricultura y tecnologías relacionadasPapa (Solanum tuberosum subsp. andígena var. pastusa suprema)Cultivo in vitroADN recombinanteProteínas recombinantesfactor de crecimiento epidérmico humano recombinante (rhEGF)Cultivo in vitroSolanum tuberosumAgrobacterium tumefaciensRecombinant proteinsin vitro cultureSolanum tuberosumAgrobacterium tumefaciensRecombinant human epidermal growth factor (rhEGF)Avances en el establecimiento de una plataforma para la producción del factor de crecimiento epidérmico humano recombinante (rhEGF) utilizando cultivos in vitro de papaAdvances in the establishment of a platform for the production of recombinant human epidermal growth factor (rhEGF) using in vitro potato culturesTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMLaReferenciaAbrahamian, P., Hammond, R. 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Molecular Biotechnology, 60(6), 387-395. https://doi.org/10.1007/s12033-018-0075-6EstudiantesInvestigadoresPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/85444/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL1152189450.2023.pdf1152189450.2023.pdfTesis de Maestría en Ciencias Agrariasapplication/pdf2860570https://repositorio.unal.edu.co/bitstream/unal/85444/2/1152189450.2023.pdfe8932efd9bb176158b96b36ddd8ca7aeMD52THUMBNAIL1152189450.2023.pdf.jpg1152189450.2023.pdf.jpgGenerated Thumbnailimage/jpeg5737https://repositorio.unal.edu.co/bitstream/unal/85444/3/1152189450.2023.pdf.jpga3e9edada1a770cb68e8ef3079caee28MD53unal/85444oai:repositorio.unal.edu.co:unal/854442024-08-21 23:13:03.575Repositorio Institucional Universidad Nacional de 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