HYBRID PEPTIDES FOR SELECTIVE TRANSPORT AND DELIVERY OF THERAPEUTIC PROTEINS (Q3212477): Difference between revisions
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HYBRID PEPTIDES FOR SELECTIVE TRANSPORT AND DELIVERY OF THERAPEUTIC PROTEINS | |||
Revision as of 08:12, 12 October 2021
Project Q3212477 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | HYBRID PEPTIDES FOR SELECTIVE TRANSPORT AND DELIVERY OF THERAPEUTIC PROTEINS |
Project Q3212477 in Spain |
Statements
116,160.0 Euro
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145,200.0 Euro
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80.0 percent
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1 January 2018
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31 December 2020
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UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
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42°52'49.51"N, 8°32'45.10"W
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15078
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UN BUEN VEHICULO DE ENTREGA INTRACELULAR DEBERIA SER EFICIENTE Y SELECTIVO. ESTAS DOS CARACTERISTICAS CONSTITUYEN UNA CONTRADICCION INTRINSECA EN EL CASO DE LOS PEPTIDOS DE PENETRACION CELULAR (CPPS). SI UN PEPTIDO EN PARTICULAR ES UN TRANSLOCADOR DE MEMBRANA MUY POTENTE, ESTE PEPTIDO NO SERA CAPAZ DE DISCRIMINAR ENTRE DISTINTAS CELULAS O TEJIDOS. ESTE CONCEPTO TAN SENCILLO ES, SIN EMBARGO, EL RESPONSABLE DE LAS ENORMES LIMITACIONES QUE PRESENTAN LOS CPPS PARA SU ADMINISTRACION POR VIA ORAL O INTRAVENOSA. LAS FORMULACIONES ACTUALES CON CPPS SE LIMITAN AL USO TOPICO, COMO ES EL CASO DE PSORBAN (PARA LA PSORIASIS) O TRANSMTS (PARA LA HIPERHIDROSIS). EL DESARROLLO DE NUEVAS RUTAS CONCEPTUALES PARA LA ACTIVACION SELECTIVA DE LOS CPPS EN EL LUGAR ADECUADO EN EL MOMENTO PRECISO, SIN DUDA POTENCIARA SU DESARROLLO CLINICO Y CONTRIBUIRA A REDUCIR LOS CORRESPONDIENTES EFECTOS SECUNDARIOS DE LOS AGENTES CITOTOXICOS, TERAPEUTICOS Y DE DIAGNOSTICO DE NUEVA GENERACION. EN ESTE PROYECTO, PROPONEMOS LA SINTESIS DE ESQUELETOS PEPTIDICOS CON LIGANDOS CON DISTRIBUCION TOPOLOGICAMENTE CONTROLADA PARA EL RECONOCIMIENTO MULTIVALENTE DE PROTEINAS DE MEMBRANA Y EL RECONOCIMIENTO SELECTIVO DE CELULAS. TAMBIEN SE ESTUDIARA LA APLICACION DE NANOPARTICULAS PEPTIDICAS PARA LA INTERNALIZACION DIRECTA DE LA RIBONUCLEOPROTEINA CAS9 PARA SU USO EN EDICION GENICA. ESTAS ESTRUCTURAS HIBRIDAS SUPRAMOLECULARES COMBINARAN EL RECONOCIMIENTO DINAMICO DE PROTEINAS CON LA INTERNALIZACION DEL PEPTIDO PARA DIVERSAS APLICACIONES, COMO EL TRANSPORTE DE PROTEINAS, LA SELECTIVIDAD CELULAR Y LA PRESENTACION MULTIVALENTE DE GLICANOS EN LIPOSOMAS. CON ESTA INVESTIGACION MULTIDISCIPLINAR, PRETENDEMOS REVOLUCIONAR EL CAMPO DEL TRANSPORTE A TRAVES DE MEMBRANAS AL IMPLEMENTAR, EN UNA UNICA MOLECULA, SELECTIVIDAD CELULAR Y PENETRACION EFICIENTE, DOS FUERZAS OPUESTAS QUE CONSTITUYEN LOS DOS PRINCIPALES RETOS A SUPERAR PARA LA APLICACION DE LOS CPPS EN LA ADMINISTRACION DE FARMACOS Y PROTEINAS TERAPEUTICAS. (Spanish)
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A GOOD DELIVERY VEHICLE SHOULD BE EFFICIENT AND SELECTIVE. THESE TWO FEATURES CONSTITUTE AN INTRINSIC BIOCHEMICAL CONTRADICTION FOR CELL PENETRATING PEPTIDES (CPPS). IF A PARTICULAR PEPTIDE IS A VERY POTENT MEMBRANE TRANSLOCATOR, THIS PEPTIDE WILL NOT BE ABLE TO DISTINGUISH BETWEEN DIFFERENT CELLS OR TISSUES. THIS NAIVE CONCEPT IS HOWEVER RESPONSIBLE FOR THE DRAMATIC LIMITATIONS OF CPPS FOR INTRAVENOUS AND ORAL ADMINISTRATION PATHWAYS. CURRENT CPPS FORMULATIONS ARE CLINICALLY RESTRICTED TO TOPICAL DOSAGE, AS EXEMPLIFIED FOR PSORBAN (FOR PSORIASIS) AND TRANSMTS (FOR HYPERHIDROSIS). THE DEVELOPMENT OF NEW CONCEPTUAL ROUTES TO SELECTIVELY ACTIVATE CPPS IN THE RIGHT PLACE AT THE RIGHT MOMENT WILL DEFINITIVELY ENHANCE THEIR CLINICAL DEVELOPMENT AND THEREFORE REDUCE THE CORRESPONDING SIDE EFFECTS OF THE NEXT GENERATION PROBES, THERAPEUTICS AND CYTOTOXIC AGENTS. WE PROPOSE THE SYNTHESIS OF PENETRATING PEPTIDE SCAFFOLDS WITH TOPOLOGICALLY CONTROLLED LIGANDS FOR MULTIVALENT MEMBRANE PROTEIN RECOGNITION AND CELL TARGETING. WE ALSO PROPOSE THE APPLICATION OF PENETRATING PEPTIDE NANOPARTICLES FOR THE DIRECT DELIVERY OF CAS9 RIBONUCLEOPROTEIN AND EFFICIENT GENE EDITION. THESE HYBRID SUPRAMOLECULAR ARCHITECTURES WILL COMBINE PEPTIDE PENETRATION AND DYNAMIC PROTEIN RECOGNITION FOR MULTIPLE APPLICATIONS SUCH AS PROTEIN TRANSPORT, CELL TARGETING AND THE MULTIVALENT PRESENTATION OF GLYCAN IN LIPOSOMES. WITH THIS MULTIDISCIPLINARY RESEARCH EFFORT WE WILL SHAKE THE FIELD OF MEMBRANE TRANSPORT BY IMPLEMENTING, IN A SINGLE MOLECULE, PENETRATION EFFICIENCY AND CELLULAR SELECTIVITY, TWO OPPOSING FORCES THAT CONSTITUTE THE TWO MAJOR CHALLENGES TO OVERCOME FOR CELL PENETRATING PEPTIDES IN DRUG DELIVERY AND PROTEIN THERAPEUTICS. (English)
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Santiago de Compostela
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Identifiers
SAF2017-89890-R
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