- Extracellular vesicles in disease
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Genetic Neurodegenerative Diseases
- Circular RNAs in diseases
- Cell Adhesion Molecules Research
- Advanced biosensing and bioanalysis techniques
- Complement system in diseases
- Exercise and Physiological Responses
- Digestive system and related health
- Virus-based gene therapy research
- 3D Printing in Biomedical Research
- Galectins and Cancer Biology
- RNA Research and Splicing
- Thermal properties of materials
- Reproductive System and Pregnancy
- Mitochondrial Function and Pathology
- Advanced Nanomaterials in Catalysis
- Neurological disorders and treatments
- Nutrition, Genetics, and Disease
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Neurogenetic and Muscular Disorders Research
- Muscle Physiology and Disorders
- Cancer Research and Treatments
University of Oxford
2019-2024
John Radcliffe Hospital
2023
Stab Vida (Portugal)
2023
University of Coimbra
2012-2018
The present work aimed at the development and application of a lipid-based nanocarrier for targeted delivery nucleic acids to glioblastoma (GBM). For this purpose, chlorotoxin (CTX), peptide reported bind selectively glioma cells while showing no affinity non-neoplastic cells, was covalently coupled liposomes encapsulating antisense oligonucleotides (asOs) or small interfering RNAs (siRNAs). resulting nanoparticles, designated CTX-coupled stable acid lipid particles (SNALPs), exhibited...
Abstract Extracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication, and potential as drug delivery vehicles. Here we demonstrate a role for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) EV assembly secretion. We observe high levels of GAPDH binding to outer surface EVs via phosphatidylserine motif (G58), which promotes extensive clustering. Further studies Drosophila biogenesis model reveal that is required normal...
Multiple studies have described extracellular microRNAs (ex-miRNAs) as being remarkably stable despite the hostile environment, when stored at 4ºC or lower. Here we show that many ex-miRNAs are rapidly degraded incubated 37ºC in presence of serum (thereby simulating physiologically relevant conditions). Stability varied widely between miRNAs, with half-lives ranging from ~1.5 hours to more than 13 hours. Notably, ex-miRNA calculated two different biofluids (murine and C2C12 mouse myotube...
AR isoform 2–encoded variant acts as a transcriptional modulator of genomic activity and is target for therapy SBMA.
Extracellular vesicles (EVs) have been implicated in the regulation of myogenic differentiation. C2C12 murine myoblast differentiation was reduced following treatment with GW4869 or heparin (to inhibit exosome biogenesis and EV uptake, respectively). Conversely, myotube-conditioned medium enhanced Ultrafiltration-size exclusion liquid chromatography (UF-SEC) used to isolate EVs non-EV extracellular protein parallel from myoblast- medium. UF-SEC-purified promoted at low doses (≤2 × 108...
The extracellular environment consists of a plethora molecules, including miRNA that can be secreted in association with vesicles (EVs) or soluble protein complexes (non-EVs). Yet, interest therapeutic short RNA carriers lies mainly EVs, the vehicles conveying great majority biological activity. Here, by overexpressing and shRNA sequences parent cells using size exclusion liquid chromatography (SEC) to separate secretome into EV non-EV fractions, we saw >98% overexpressed was within...
Abstract CD8 + T lymphocytes play vital roles in killing infected or deranged host cells, recruiting innate immune and regulating other aspects of responses. Like any cell, cells also produce extracellular particles. These include vesicles (EVs) non‐vesicular particles (NVEPs). cell‐derived EVs are proposed to mediate cell‐to‐cell signalling, especially the context inflammatory responses, autoimmunity, infectious diseases. supramolecular attack (SMAPs), which same size range as a component...
Abstract Extracellular vesicles (EVs) have recently emerged as a highly promising cell-free bio-therapeutics. While range of engineering strategies been developed to functionalize the EV surface, current approaches fail address limitations associated with endogenous surface display, pertaining heterogeneous display commonly used EV-loading moieties among different subpopulations. Here we present novel platform multiple protein therapeutics simultaneously on surface. As proof-of-concept,...
Abstract Extracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication and pathophysiology. Their capacity to transfer biomolecules between cells has sparked efforts bioengineer EVs as drug delivery vehicles. However, a better understanding of EV biogenesis mechanisms function is required unleash their considerable therapeutic potential. Here we demonstrate novel role for GAPDH, glycolytic enzyme, assembly secretion, exploit these findings...
Abstract Extracellular vesicles (EVs) hold great promise as therapeutic delivery vehicles, although their potential is limited by a lack of efficient EV engineering strategies to enhance loading and functional cargo. Here, we identified N-glycosylation putative EV- sorting feature using novel bioinformatics analysis strategy. We exploited this finding develop platform for EV-mediated macromolecular cargoes based on PTTG1IP, small N- glycosylated, single spanning transmembrane protein....
Abstract Background The −13910 C/T single nucleotide polymorphism located within the MCM6 gene, an enhancer region upstream of lactase-phlorizin hydrolase is associated with lactase persistence/non-persistence traits among Caucasian population. performance a new point-of-care CE-IVD (In Vitro Diagnostic) marked isothermal lab-on-phone lactose intolerance assay, using crude samples, was assessed in comparison Sanger sequencing purified DNA, as reference method. Methods study conducted...
Abstract CD4 T helper cells (TH cells) play a vital role in coordinating and amplifying the immune response to specific pathogens. They constitutively produce different kinds of extracellular vesicles (EVs), which mediate cell-to cell communication diverse roles regulation inflammatory processes. Here we provide resource documenting composition activated TH EVs demonstrating their ability instigate pro-inflammatory antigen-presenting (APCs). were characterized by lipidomics, proteomics,...
Machado-Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide and caused by over-repetition of a CAG tract in coding region ATXN3/MJD1 gene, which confers toxic gain-of-function to ataxin-3 protein resulting degeneration within different brain regions, particularly cerebellum. There currently no available treatment modify progression. The direct approach treat MJD block production mutant using silencing sequences. Our group others already showed that mouse models...