A5054300827- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- HIV Research and Treatment
- Virology and Viral Diseases
- Advanced biosensing and bioanalysis techniques
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- 3D Printing in Biomedical Research
- Advanced Drug Delivery Systems
- Graphene and Nanomaterials Applications
- Barrier Structure and Function Studies
- Advanced Biosensing Techniques and Applications
- vaccines and immunoinformatics approaches
- Innovative Microfluidic and Catalytic Techniques Innovation
- Protein purification and stability
- thermodynamics and calorimetric analyses
- Cancer Research and Treatments
- Immune Response and Inflammation
- Biosensors and Analytical Detection
- Molecular Communication and Nanonetworks
- Click Chemistry and Applications
- Field-Flow Fractionation Techniques
- Carbon Nanotubes in Composites
Massachusetts Institute of Technology
2021-2025
Broad Institute
2024
Center for Research in Molecular Medicine and Chronic Diseases
2017-2022
Universidade de Santiago de Compostela
2017-2022
The blood–brain barrier represents a significant challenge for the treatment of high-grade gliomas, and our understanding drug transport across this critical biointerface remains limited. To advance preclinical therapeutic development there is an urgent need predictive in vitro models with realistic blood–brain-barrier vasculature. Here, we report vascularized human glioblastoma multiforme (GBM) model microfluidic device that accurately recapitulates brain tumor vasculature self-assembled...
Rapid advances in nucleic acid therapies highlight the immense therapeutic potential of genetic therapeutics. Lipid nanoparticles (LNPs) are highly potent nonviral transfection agents that can encapsulate and deliver various therapeutics, including but not limited to messenger RNA (mRNA), silencing (siRNA), plasmid DNA (pDNA). However, a major challenge targeted LNP-mediated systemic delivery is nanoparticles’ nonspecific uptake by liver mononuclear phagocytic system, due partly adsorption...
The development of an effective HIV vaccine continues to be a major health challenge since, so far, only the RV144 trial has demonstrated modest clinical efficacy. Recently, targeting 12 highly conserved protease cleavage sites (PCS1–12) been presented as strategy seeking hamper maturation and infectivity HIV. To pursue this line research, because peptide antigens have low immunogenicity, we included these peptides in engineered nanoparticles, aiming at overcoming limitation. More...
Effective delivery of drug and gene cargos to hematopoietic stem progenitor cells (HSPCs) is a major challenge. Current therapeutic strategies in genetic disorders or hematological malignancies are hindered by high costs, low accessibility, off-target toxicities. Layer-by-layer nanoparticles (LbL NPs) modular systems with tunable surface properties enable highly specific targeting. In this work, we developed LbL NPs that target HSPCs via antibody functionalization reduced uptake circulating...
Background: Tumor-associated macrophages (TAMs), with M2-like immunosuppressive profiles, are key players in the development and dissemination of tumors. Hence, induction M1 pro-inflammatory anti-tumoral states is critical to fight against cancer cells. The activation endosomal toll-like receptor 3 by its agonist poly(I:C) has shown efficiently drive this polarization process. Unfortunately, presents significant systemic toxicity, clinical use restricted a local administration. Therefore,...
Abstract Research efforts towards cancer therapeutics have resulted in the development of a variety pharmacological molecules, including small synthetic molecules and biological drugs (RNA‐based therapies monoclonal antibodies—mAbs), intended to target tumor or immune‐related cells, their signaling mediators. The majority them present important biopharmaceutical problems related difficulties for overcoming barriers reach targets. Nanotechnology has been, more than 60 years, trying solve...
HIV mutates rapidly and infects CD4+ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we testing novel candidate the 12 protease cleavage sites (PCSs) (the PCS vaccine), comparison with full-length Gag Env Gag/Env vaccine) Mauritian cynomolgus macaque/SIV model. In this study...
After over 3 decades of research, an effective anti-HIV vaccine remains elusive. The recently halted HVTN702 clinical trial not only further stresses the challenge to develop HIV but also emphasizes that unconventional and novel strategies are urgently needed. Here, we report a focusing immune response on sequences surrounding 12 viral protease cleavage sites (PCSs) provided greater than 80% protection Mauritian cynomolgus macaques against repeated intravaginal SIVmac251 challenges....
Effective delivery of drug and gene cargos to hematopoietic stem progenitor cells (HSPCs) is a major challenge. Current therapeutic strategies in genetic disorders or hematological malignancies are hindered by high costs, low accessibility, off-target toxicities. Layer-by-Layer nanoparticles (LbL NPs) modular systems with tunable surface properties enable highly specific targeting. In this work, we developed LbL NPs that target HSPCs via antibody functionalization reduced uptake circulating...
Studies have shown that vaccine vectors and route of immunization can differentially activate different arms the immune system. However, effects HIV immunogens on mucosal inflammation not yet been studied. Because sites are primary infection, we evaluated cervico-vaginal inflammatory cytokine chemokine levels Mauritian cynomolgus macaques following boost using two SIV immunogens. The PCS delivers 12 20-amino acid peptides overlapping protease cleavage sites, Gag/Env full Gag Env proteins...
High grade gliomas (HGG) are the most common malignant brain tumor in children, and remain effectively incurable with 5 year overall survival. We developed a library of functionalized nanoparticles (NPs) ligands targeting BBB shuttle mechanisms. Using layer-by-layer (LbL) platform to functionally ‘wrap’ polyelectrolytes around NP core by iterative electrostatic adsorption, we can incorporate wide range drugs, modulate release kinetics, add moieties highly tunable system. In this study,...
Abstract The blood-brain barrier represents a significant challenge for the treatment of high-grade gliomas, and our understanding drug transport across this critical biointerface remains limited. To advance preclinical therapeutic development there is an urgent need predictive in vitro models with realistic vasculature. Here, we report vascularized human glioblastoma (GBM) model microfluidic device that accurately recapitulates brain tumor vasculature self-assembled endothelial cells,...
Abstract After over three decades of research, an effective anti-HIV vaccine remains elusive. Unconventional and novel strategies are needed. Here, we report that a focusing the immune response on sequences surrounding 12 viral protease cleavage sites (PCSs) provides greater than 80% protection Mauritian cynomolgus macaques (MCMs) against repeated intravaginal SIVmac251 challenges. The PCS-specific T cell responses correlated with efficacy. PCS does not induce activation inflammation known...
Abstract Platinum-based agents remain a key component of therapy for children with medulloblastoma, despite significant systemic side effects and only modest blood-brain barrier (BBB) penetration. Cisplatin has cerebrospinal fluid-to-plasma ratio <5% dose-limiting nephrotoxicity, ototoxicity, myelosuppression. Improving delivery cisplatin across the BBB selectively accumulating in tumors could improve its therapeutic index. To this end, we are leveraging chemical engineering techniques to...
<h3>Background</h3> Pre-clinical models are crucial for better understanding and treating human diseases such as cancer. Autochthonous of lung cancer excellent tools to study tumor progression evolution. However, current approaches rely on intra-tracheal, viral delivery Cre recombinase initiate tumorigenesis by activating oncogenes deleting suppressor genes.<sup>1</sup> Two caveats this technique the lack cell-type specificity vectors resulting immunogenicity these vectors. We have...