grupo

Group name: Gene and Cell Therapy

    Group leader
  • Francisco Martín Molina
  • Senior Researcher
  • Marién Cobo Pulido
  • Karim Benabdel Lah El Khlanji
  • Pilar Muñoz Fernández
  • PHD Students
  • Eliana Barriocanal Casado
  • Almudena Sánchez Gilabert
  • Sabina Sánchez Hernández
  • María Tristán Manzano
  • Technicians
  • Darío Abril García
  • Internships
  • María Rocio Martín Guerra
  • Juan José Rodríguez Sevilla
  • Iciar Beraza Gómez

Presentation Video

SCIENTIFIC INTEREST AREAS

Gene and Cell Therapy The general aim of this area is the development of new therapeutic strategies for severe diseases by combining adult stem cells and gene transfer Technologies.

Adult stem cells (such as mesenchymal stem cells-MSC) have several properties that make them very attractive for therapy of multiple diseases. In particular their immunomodulatory, secretory and migratory capabilities are of special interest for our Group.

Gene therapy involves the intoduction of genes into cells with therapeutic means. The tools available to deliver the trasngenes are known as gene therapy vectors. We are working with gene therapy vectors derived from HIV-1, one of the most efficient and safe gene delivery vectors for stable expression

RESEARCH AREAS

  • Design of safer and more efficient gene transfer vectors for Gene Therapy applications. In this direction, we are interested in:

    1-       Lentiviral vectors.

    1. The development of doxycycline-inducible lentiviral vectors based on the original TetR repressor in the absence of transactivators.
    2. To optimize LVs in order to increase stability and reduce genotoxicity (insulators).
    3. To develop physiologically regulated LVs..
    4. To generate human cellular models to study LVs behavior.

    2-       Genome edition using specific nucleases (SNs) (zinc finger nucleases (ZFNs) y CRISPR/Cas9).

    1. Optimization of SNs delivery into hematopoietic stem cells (HSCs) and T cells.
    2. Donor DNA designs for improved homologous recombination dependent (HRD) genome edition.
    3. Alternative system for genome edition independent of HRD.

     

  • Translation of gene transfer vector technology into clinical applications for rare diseases and cancer. We collaborate with several research institutions, Hospitals and patients association in order to translate our technology to the patients. In particular, we are interested in the development of gene-cell therapy strategies for the treatment of:

    1-       Wiskott-Aldrich Syndrome (WAS). We are developing new strategies based on physyologically regulated LVs expressing the correct form of the affected gene (WAS). We are also studying the possibility to implement genome edition as an alternative to lentiviral vectors. We have developed the first WAS pluripotent cellular model for preclinical studies of these therapeutic strategies.

    2-       Pompe disease and CoQ deficiency. We aim the development of gene-modified HSCs that over-express the GAA or Coq9 genes as an approach to deliver these proteins into the affected tissues.

    3-       Progressive multiple sclerosis. Our strategy consists in the development of mesenchymal stromal cells with improved immunomodulatory and neuroprotective therapeutic activities by expressing different genes.

    4-       Limphomas ad Type B leukemias. The strategy is to develop doxycycline inducible CARs-T cells in order to avoid the depletion of B cells during this impressive strategy. We are also interested in modulate CARs expression levels in order to improved efficacy and to reduce secondary effects. 

TECHNOLOGY PLATFORMS

  • Confocal Microscopy
  • Vector development
  • Cell sorting y FACS analysis
  • Animal facilities
  • Radioactivity
  • Cell Culture
  • Sequencing
  • Molecular cloning
  • Cell biology In vivo imaging
  • Producción vectores Lentivirales
  • Knock-out y knock-in de genes mediante edición genómica (Zinc-Finger Nucleases y Sistema CRISPR/Cas9).

FUNDING

  • Instituto de Salud Carlos III
  • Consejería de Economía, Innovación y Ciencia de la Junta de Andalucía
  • Consejería de Salud de la Junta de Andalucía
  • Iniciativa Andaluza de Terapias Avanzadas y la Fundación Progreso y Salud

SELECTED PUBLICATIONS

- Eliana Barriocanal-Casado, Cristina Cueto-Ureña, Karim Benabdellah, Alejandra Gutiérrez-Guerrero, Marién Cobo, Agustín Hidalgo-Gutiérrez, Juan José Rodríguez-Sevilla, Luis C. López* and Francisco Martín*. *Share senior authorship. Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9R239X Mice.: PlosOne 11(6): e0158344: Año: 2016. . I Impacto: 3.5

- Toscano MG, Muñoz P, Sánchez-Gilabert A, Cobo M, Benabdellah K, Anderson P, Ramos-Mejía V, Real PJ, Neth O, Molinos A, Gregory PD, Holmes MC, Martin F. Absence of WASp Enhances Hematopoietic And Megakaryocytic Differentiation In A Human Embryonic Stem Cell Model. Molecular Therapy. Volumen: 24(2) Páginas: 342-353 Fecha: 2016 . I Impacto: 6,4

- Carrillo-Gálvez AB, Cobo M, Cuevas-Ocaña S, Gutierrez-Guerrero A, Sanchez-Gilabert, Bogarzole P, García-Perez A, Muñoz P, Benabdellah K, Toscano MG, Anderson P* and Martin F*. * Share senior and corresponding authorship Mesenchymal stem cells (MSCs) bind Transforming Growth Factor (TGF)-b1 to their surface through the expression of GARP: Effects on MSC biology and immunomodulation Stem Cells Volumen: 33(1) Páginas, 183-195 Fecha: enero 2015 I Impacto: 7.1

- Miguel G. Toscano1,b, Oscar Navarro-Montero1#, Veronica Ayllon1#, Veronica Ramos-Mejia1, Clara Bueno1,2, Tamara Romero1, Marien Cobo1, Pablo Menendez1,2,3*, Pedro J. Real1* and Francisco Martin1* *Share senior authorship

SCL/TAL1 enhances megakaryocytic specification of human embryonic stem cells by activating a megakaryocyte-specific transcriptional network. Molecular Therapy. Volumen: 23(1) Páginas 158-70 Fecha: Jan 2015 . I Impacto: 6,4

- Hernández-Cortés P, Toledo-Romero MA, Delgado M, Clara E. Sánchez-González, Martin F, Galindo-Moreno P, O’Valle F. PERIPHERAL NERVE RECONSTRUCTION WITH EPSILONCAPROLACTONE CONDUITS SEEDED WITH VASOACTIVE INTESTINAL PEPTIDE GENE-TRANSFECTED MESENCHYMAL STEM CELLS IN A RAT MODEL..Journal of Neural Engineering. Vol: 11(4) 046024 Fecha: agosto 2014 . I Impacto: 3,4

- Amelia Escolano, Sara Matrinez Martinez, Arantzazu Alfranca, Katia Urso, Helena Maria Izquierdo, Mario Delgado, Francisco Martin, Guadalupe Sabio, David Sancho, Pablo Gomez-del Arco and Juan Miguel Redondo. Specific calcineurin-targeting in macrophages confers resistance to inflammation via MKP-1 and p38 EMBO J. Vol: 16;33(10) Páginas 1117-33 Fecha: Mayo 2014 . I Impacto: 10.7

- Benabdellah K, Gutierrez-guerrero A, Cobo M, Muñoz P, and Martin F A Chimeric HS4-SAR insulator (IS2) that prevents silencing and enhances expression of lentiviral vectors in pluripotent stem cells PlosOne Volumen: 9(1) Páginas: e84268 Fecha: Enero 2014 . I Impacto: 4,4

- Anderson P, Carrillo-Gálvez AB, García-Perez A, Cobo M, Martin F CD105 (Endoglin)-Negative Murine Mesenchymal stromal cells define a New Multipotent Subpopulation with Distinct Differentition and immunomodulatory properties. PlosOne. Vol: 8(10) Páginas: e76979 Fecha: October 2013 . I Impacto: 4,4

- MG Toscano, P. Anderson, P Muñoz, K. Benabdellah, M. Cobo G Lucena, PD Gregory, M Holmes and F. MartinUse of Zinc-Finger Nucleases to Knock Out the WAS Gene in K562Cells: a human cellular model for Wiskott-Aldrich syndrome Disease Models & Mechanisms Vol: 6 Páginas: 544-54 Fecha: 2013 I Impacto: 4,9

- Cobo M, P Anderson P, Benabdellah K, MG Toscano M, Muñoz P, García-Perez A, Gutierrez I, Delgado M., Martin F Mesenchymal stem cells expressing vasoactive intestinal peptide ameliorate symptoms in a model of chronic multiple sclerosis. Cell Transplantation. Volumen: 22 Páginas: 839 -54 Fecha: 2013 I Impacto: 3.5

- Benabdellah K, Cobo M, Muñoz P, Toscano MG and Martin F* Development of an all-in-one Lentiviral vector system based on the original TetR for the easy generation of Tet-ON cell lines. Plos One. Volumen: 6(8) Páginas: e23734 Fecha: 2011 I Impacto: 4,4

RESEARCH GROUP PATENTS

1- AUTHORS: Francisco Martin, Pilar Muñoz, Karim Benabdellah, MiguelG. Toscano, Pilar Muñoz y Marién Cobo.

TITLE: HIGHLY INDUCIBLE TET-ON VECTOR SYSTEM

APPLICATION No: PCT / EP2012 / 059408

YEAR: 2011

INSITITUTION. Fundación progreso y Salud (FPS)

COUNTRIES: Europa: EP12727326.6 EEUU: US14/118,880

Licenced to Canvax Biotech

Freedom to aperate in all the world but:

EEUU. Freedom to aperate from 26th June 2017

Canadá, Japón, Reino Unido, Francia, Alemania, Lituania y Suiza Freedom to aperate from 26th June 2018

2- AUTHORS: Francisco Martin, Pilar Muñoz, Karim Benabdellah, MiguelG. Toscano,

TITLE: Lentiviral vector for identification of hematopoietic cells

APPLICATION No: P201230449

YEAR: 2012

INSITITUTION. Fundación progreso y Salud (FPS)

COUNTRY: Spain. Abandoned in 2015

3- AUTHORS: Francisco Martin, Karim Benabdellah, Pilar Muñoz, Alejandra Gutierrez Guerrero, Marien Cobo.

TITLE: Insulator to improve gene transfer vectors

APPLICATION No: PCT/EP2014/055027 Año: 2014

INSITITUTION: Fundación progreso y Salud (FPS)

COUNTRIES: Europa EP 14716525.2 EEUU: US14/776,008

4- AUTHORS: Per Anderson, Francisco Martin, Ana Carrillo, Marién Cobo.

TITLE: CD105-Negative Multipotent Mesenchymal Stromal Cells

APPLICATION No: EP13382338.5

YEAR: 2014

INSITITUTION. Fundación progreso y Salud (FPS)

COUNTRY: Europe PCT/EP2014/067996

5- AUTHORS: Pedro Real Luna, Miguel G. Toscano, Pablo Menendez Bujan, Francisco Martin Molina, Oscar Montero Navarro, Verónica Ayllón Cases, Verónica Ramos Mejía, Clara Bueno Uroz, Marién Cobo Pulido, TamaraRomero Escobar.

TITLE: Method for generation of megakaryocites and platelets

APPLICATION No: P201331568

YEAR: 2014

INSITITUTION. Fundación progreso y Salud (FPS)

COUNTRY: Spain

6- AUTHORS: Per Anderson, Francisco Martin Molina, Ana Belén Carrillo-Gálvez, Marién Cobo Pulido, Angélica García-Perez.

TITLE: New surface marker for the identification of mesenchyal stem cells.

APPLICATION No: P201331730

YEAR: 2016

INSITITUTION. Fundación progreso y Salud (FPS)

COUNTRY: Spain .PCT/ES2014/070874

7- AUTHORS: Luis Carlos Lopez, Francisco Martin Molina, Eliana Barriocanal Casado, Karim Benabdellah Khlanji, Marien Cobo Puldo, Cristina Cueto Ureña,.

TITLE: Use of Coenzyme Q biosenthetic proteins

APPLICATION No: P201630630

YEAR: 2016

INSITITUTIONS. Fundación progreso y Salud (FPS) y Universidad de Granada

COUNTRY: Spain

ADDITIONAL INFORMATION

Collaborations:

  • Michael Holmes. Senior Director at Sangamo BioSciences, Inc. Richmond, California 94804, USA
  • Prof Juan Miguel Redondo . Director of the Biología Vascular e inflamación Department. Centro Nacional de Investigaciones Cardiovasculares (CNIC)
  • Professor Adrian Thrasher. Wellcome Trust Senior Clinical Fellow. Director of Centre for Immunodeficiency. Director of Gene Therapy Programme Institute of Child Health (UCL)
  • Prof Juan Bueren. Director del programa de terapia génica en células hematopoyéticas. Terapias innovadoras en el sistema hematopoyético. CIEMAT. Madrid.
  • Inmaculada Herrera Arroyo . Directora U.G.C. hematología. Hospital Reina Sofía. IMIBIC. Directora de la Unidad de terapia celular. Córdoba
  • Dr Els Verhoeyen. Principal investigator. Director Human Virology Department. INSERN. ENLS. Lyon, France.
  • Professor Mary Collins . Dean, Faculty of Life Sciences University College London. London (UCL), UK.
  • Olaf Neth, Agueda Molinos. U.G.C. de hematología y hemoterapia. Instituto de Biomedicina de Sevilla. Hospital Virgen del Rocío, Sevilla
  • Oscar Fernández y Margarita Suardiaz . U.G.C de Neurociencias, Instituto de Biomedicina de Málaga. HU Regional de Málaga y Virgen de la Victoria.
  • José Antonio Pérez Simón. Director UGC Hematología. Hospital Virgen del Rocío
  • Prof. Mario Delgado . Profesor de investigación. Director del IPB López Neyra. CSIC. Granada.
  • Dr Ignacio Molina . Vicerrector de investigación PTS. CIBM. Profesor Inmunología Universidad de Granada.
  • Dr Jose Carlos Segovia. Jefe de Unidad. Terapias innovadoras en el sistema hematopoyético. CIEMAT
  • Francisco Abadía. Biología celular Department. Granada University
  • Elier Paz Rojas. CEO. Canvax Biotech. Córdoba
  • Pedro J. del Real . IP Gene Regulation, stem cells and development group. GENYO

BOOKS AND CHAPTERS

- EDITOR

1-BOOK: Gene Therapy-Tools and Potential Applications. Francisco Martin (Ed.)

Ref ISBN : 978-953-51-1014-9,

DOI : 10.5772/50194 FECHA: Febrero 2013

Editorial InTech , Open Access Available from: http://www.intechopen.com/books/gene-therapy-tools-and-potential-applications

All Chapters download: 63.040

Times cited (Web of Science): 13

- BOOK CHAPTERS

1-Autores F. Martin , K. Benabdellah, M. Cobo, P. Muñoz, P Anderson MG Toscano

Capitulo : New Vectors for Stable and Safe Gene Modification,

Libro: Gene Therapy - Developments and Future Perspectives . Chunsheng Kang (Ed.)

Ref ISBN : 978-953-307-617-1,

DOI : 10.5772/748 FECHA Junio 2011

Editorial InTech , Available from: http://www.intechopen.com/articles/show/title/new-vectors-for-stable-and-safe-gene-modification

Chapter download: 4343

2-Autores F. Martin , K. A. Gutierrez- Guerrero, K. Benabdellah

Capitulo : Gene Therapy for primary Immunodeficiencies

Libro: Gene Therapy-Tools and Potential Applications. Francisco Martin (Ed.)

Ref ISBN : 978-953-51-1014-9,

DOI : 10.5772/50194 FECHA: Febrero 2013

Editorial InTech , Open Access Available from: http://www.intechopen.com/books/gene-therapy-tools-and-potential-applications/gene-therapy-for-primary-immunodeficiencies

Chapter download: 1796

3-Autores F. Martin , K. A. Gutierrez- Guerrero, K. Benabdellah

Capitulo : Gene Delivery Technologies for Efficient Genome Editing: Applications in Gene Therapy

Libro: Modern Tools for Genetic Engineering

Ref ISBN : 978-953-51-2234-0. Print ISBN 978-953-51-2392-7

DOI : 10.5772/50194 FECHA: May 2016

Editorial InTech , Open Access Available from: www.intechopen.com/books/modern-tools-for-genetic-engineering

Chapter download: 119

COMMITTEES

Activity: Agencia Nacional de Evaluación y Prospectiva (ANEP)

Entity:: Ministerio de Educación y Ciencia Activity: Project Reviewer

Start date: 2005 End date: --

Activity: Academic commission Biomedicine doctorade programme

Entidad: Granada University Type of entity: University

Start date: 2012 End date: --

Activity: Commission for the evaluation of Biomedicne doctarade students

Entidad: Granada University Type of entity: University

Start date: 2012 End date: --

Activity: Commission for the evaluation of Master Thesis from the “Genetic and Evolution Master”

Entidad: Granada University Type of entity: University

Start date: 2012 End date: --

Activity: Commission for the evaluation of Master Thesis from the “Molecualr and cellular Immunology Master

Entidad: Granada University Type of entity: University

Start date: 2010 End date: --

REVIEWER FOR THE FOLLOWING JOURNALS:

- Blood

- Human Molecular Genetic

- Gene Therapy

- Human Gene Therapy

- Stem Cell Research & Therapy

- Journal of Gene Medicine

- PlosOne

- Cell Transplantation

- BMC Biotechnology

- Molecular Genetics and Genomics

- Journal of nanoparticle research

- Revista de neurología

- Recent Patents on DNA and Gene Sequence

- Biotechnology Progress

- World Journal of Gastroenterology

- Journal of Pediatric Genetics

- Clinical and Experimental Immunology.

- American Journal of Life Science.

REVIEWER FOR THE FOLLOWING ORGANISMS:

- Swiss National Science Fundation. Suiza. 2002

- Plan Nacional de Investigación Científica. España (ANEP)

- Fundaçao para a ciencia e a Tecnologia (FCT). Portugal

- Agencia para la Calidad del Sistema Universitario de Castilla y León (ACSUCYL)

- Netherlands Organisation for Health Research and Development. Holanda

- Comisión de Seguimiento y Control para la Donación y Utilización de

- Células y Tejidos Humanos

- LOREAL-UNESCO. Bolsas de investigación 2010