A5101447095- Skin and Cellular Biology Research
- Silk-based biomaterials and applications
- Virus-based gene therapy research
- RNA regulation and disease
- RNA Interference and Gene Delivery
- CRISPR and Genetic Engineering
- Cell Adhesion Molecules Research
- Spectroscopy Techniques in Biomedical and Chemical Research
- Transgenic Plants and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Animal Genetics and Reproduction
- Mesenchymal stem cell research
- Health and Lifestyle Studies
- Cellular Mechanics and Interactions
- Antimicrobial Peptides and Activities
- Plant Reproductive Biology
- Wound Healing and Treatments
- Microfluidic and Capillary Electrophoresis Applications
- Advanced Fluorescence Microscopy Techniques
- Dermatological and Skeletal Disorders
- Immunotherapy and Immune Responses
- Advanced Biosensing Techniques and Applications
- Tendon Structure and Treatment
- Diet, Metabolism, and Disease
- Olfactory and Sensory Function Studies
Ação Educativa
2023
Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas
2007-2022
Hospital Universitario Fundación Jiménez Díaz
2014-2022
Centro de Investigación Biomédica en Red
2011-2022
Universidad Carlos III de Madrid
2016-2022
Centre for Biomedical Network Research on Rare Diseases
2008-2022
Instituto de Salud Carlos III
2013-2022
Instituto de Investigación de Enfermedades Raras
2017
Universidad Complutense de Madrid
2011-2017
Unidades Centrales Científico-Técnicas
2016
Highly branched poly(β-amino ester) polymers are developed to carry a gene and enter cells for the production of protein.
Designer nucleases allow specific and precise genomic modifications represent versatile molecular tools for the correction of disease-associated mutations. In this study, we have exploited an ex vivo CRISPR/Cas9-mediated homology-directed repair approach a frequent inherited mutation in exon 80 COL7A1, which impairs type VII collagen expression, causing severe blistering skin disease recessive dystrophic epidermolysis bullosa. Upon CRISPR/Cas9 treatment patient-derived keratinocytes, using...
Clonal gene therapy protocols based on the precise manipulation of epidermal stem cells require highly efficient gene-editing molecular tools. We have combined adeno-associated virus (AAV)-mediated delivery donor template DNA with transcription activator-like nucleases (TALE) expressed by adenoviral vectors to address correction c.6527insC mutation in COL7A1 gene, causing recessive dystrophic epidermolysis bullosa a high percentage Spanish patients. After transduction these viral vectors,...
Background Dystrophic epidermolysis bullosa (DEB) is a genodermatosis caused by mutations in COL7A1. The clinical manifestations are highly variable from nail dystrophy to life-threatening blistering, making early molecular diagnosis and prognosis of utmost importance for the affected families. Mutation identification mandatory prenatal testing. Objectives To conduct first mutational analysis COL7A1 Spanish cohort, assess mutation consequences at protein/mRNA level establish...
Recessive dystrophic epidermolysis bullosa is a severe skin fragility disease caused by loss of functional type VII collagen at the dermal-epidermal junction. A frameshift mutation in exon 80 COL7A1 gene, c.6527insC, highly prevalent Spanish patient population. We have implemented gene-editing strategies for frame restoration NHEJ-induced indels epidermal stem cells from patients carrying this mutation. TALEN nucleases designed to cut within sequence were delivered primary keratinocyte...
Genome-editing technologies that enable the introduction of precise changes in DNA sequences have potential to lead a new class treatments for genetic diseases. Epidermolysis bullosa (EB) is group rare disorders characterized by extreme skin fragility. The recessive dystrophic subtype EB (RDEB), which has one most severe phenotypes, caused mutations COL7A1. In this study, we report gene-editing approach ex vivo homology-directed repair (HDR)-based gene correction uses CRISPR-Cas9 system...
Using a recently described skin-humanized model based on the engraftment of human bioengineered skin equivalents onto immunodeficient mice, we compared efficacy different in vivo gene transfer strategies aimed at delivering growth factors to promote wound healing. The approaches involving transient delivery keratinocyte factor (KGF) wounds performed engrafted included (1) KGF by intradermal adenoviral injection; (2) vector immobilized fibrin carrier; and (3) KGF-adenoviral gene-transferred...
Abstract Cutaneous diabetic wounds greatly affect the quality of life patients, causing a substantial economic impact on healthcare system. The limited clinical success conventional treatments is mainly attributed to lack knowledge pathogenic mechanisms related chronic ulceration. Therefore, management ulcers remains challenging issue. Within this context, reliable animal models that recapitulate situations impaired wound healing have become essential. In study, we established new in vivo...
Junctional epidermolysis bullosa (JEB) is a debilitating hereditary skin disorder caused by mutations in genes encoding laminin-332, type XVII collagen (C17), and integrin-α6β4, which maintain stability between the dermis epidermis. We designed patient-specific Cas9-nuclease- -nickase-based targeting strategies for reframing common homozygous deletion exon 52 of COL17A1 associated with lack full-length C17 expression. Subsequent characterization protein restoration, indel composition,...
Abstract Chronic or sustained hyperglycemia associated to diabetes mellitus leads many medical complications, thus, it is necessary track the evolution of patients for providing adequate management disease that required restoration carbohydrate metabolism a normal state. In this paper, novel monitoring approach based on mm-wave spectroscopy comprehensively described and experimentally validated using living animal models as target. The measurement method has proved possibility non-invasive,...
Functional impairment or complete loss of type VII collagen, caused by mutations within COL7A1, lead to the severe recessive form skin blistering disease dystrophic epidermolysis bullosa (RDEB). Here, we successfully demonstrate RNA trans-splicing as an auspicious repair option for located in a wide range exons fully converting RDEB phenotype ex vivo pre-clinical mouse model based on xenotransplantation. Via self-inactivating (SIN) lentiviral vector 3′ molecule, capable replacing COL7A1...
Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is an autosomal recessive disorder caused by pathogenic variants in PLEC1, which encodes plectin. It characterized mild mucocutaneous fragility and blistering muscle weakness. Translational readthrough-inducing drugs, such as repurposed aminoglycoside antibiotics, may represent a valuable therapeutic alternative for untreatable rare diseases nonsense variants.To evaluate whether systemic gentamicin, at dose of 7.5 mg/kg/d 14...
Background Basal epidermolysis bullosa simplex (EBS) is a group of blistering genodermatoses mostly caused by mutations in the keratin genes, KRT5 and KRT14. Recessive represent about 5% all EBS mutations, being common specific populations with high consanguinity, where affected patients show severe phenotypes. Objectives To accomplish first mutational analysis Spanish origin to delineate comprehensive genotype–phenotype correlation. Methods Twenty-one families were analysed....
Human papillomavirus (HPV) is the causative agent of human cervical cancer and has been associated with oropharyngeal squamous cell carcinoma development. Although prophylactic vaccines have developed, there a need to develop new targeted therapies for individuals affected malignant infected lesions in these locations, which must be tested appropriate models. Cutaneous beta HPV types appear involved skin carcinogenesis. Virus oncogenicity partly achieved by inactivation retinoblastoma...
The pathological skin phenotype caused by hyperglycemia is an important indicator for the progress of diabetes mellitus. An early detection assures intervention to regulate carbohydrate metabolism. In this publication a non-invasive principle based on measurement complex scattering parameters in millimeter-wave frequency range presented. provides evidence applicability identification different glycemic states animal models. method proposed here can be used predict status models and...
A native fluorescence, portable and low-cost spectroscopic instrument for the detection of sustained hyperglycemia, a condition very often associated to diabetes mellitus, capable analyzing full blood, is presented experimentally validated.