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Biodistribution of therapeutic extracellular vesicles.
The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their unique ability to transfer macromolecules across cells and biological barriers has mad…
Activation-induced thrombospondin-4 works with thrombospondin-1 to build cytotoxic supramolecular attack particles.
Cytotoxic attack particles released by CTLs and NK cells include diverse phospholipid membrane and glycoprotein encapsulated entities that contribute to target cell killing. Supramolecular attack particles (SMAPs) are one type of particle characterized by a cytotoxic core enriched in granzymes and perforin su…
Modulation of Pro-Inflammatory IL-6 Trans-Signaling Axis by Splice Switching Oligonucleotides as a Therapeutic Modality in Inflammation.
Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a crucial role in maintaining normal homeostatic processes under the pathogenesis of various inflammatory and autoimmune diseases. This context-dependent effect from a cytokine is due to two distinctive forms of signaling: cis-signaling and trans-s…
Nanoparticle/Engineered Bacteria Based Triple-Strategy Delivery System for Enhanced Hepatocellular Carcinoma Cancer Therapy.
BACKGROUND: New treatment modalities for hepatocellular carcinoma (HCC) are desperately critically needed, given the lack of specificity, severe side effects, and drug resistance with single chemotherapy. Engineered bacteria can target and accumulate in tumor tissues, induce an immune response, and…
Antibody-displaying extracellular vesicles for targeted cancer therapy.
Extracellular vesicles (EVs) function as natural delivery vectors and mediators of biological signals across tissues. Here, by leveraging these functionalities, we show that EVs decorated with an antibody-binding moiety specific for the fragment crystallizable (Fc) domain can be used as a modular delivery system for…
Snorkel-tag based affinity chromatography for recombinant extracellular vesicle purification.
Extracellular vesicles (EVs) are lipid nanoparticles and play an important role in cell-cell communications, making them potential therapeutic agents and allowing to engineer for targeted drug delivery. The expanding applications of EVs in next generation medicine is still limited by existing tools for scaling sta…
Surface display of functional moieties on extracellular vesicles using lipid anchors.
Extracellular vesicles (EVs) are efficient natural vehicles for intercellular communication and are under extensive investigation for the delivery of diverse therapeutics including small molecule drugs, nucleic acids, and proteins. To understand the mechanisms behind the biological activities of EVs and develop…
Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading.
Extracellular vesicles (EVs) are gaining increasing attention for diagnostic and therapeutic applications in various diseases. These natural nanoparticles benefit from favorable safety profiles and unique biodistribution capabilities, rendering them attractive drug-delivery modalities over synthetic analogs. Ho…
An extracellular vesicle delivery platform based on the PTTG1IP protein.
Extracellular vesicles (EVs) are promising therapeutic delivery vehicles, although their potential is limited by a lack of efficient engineering strategies to enhance loading and functional cargo delivery. Using an in-house bioinformatics analysis, we identified N-glycosylation as a putative EV-sorting feature. PTT…
Tissue-specific modulation of CRISPR activity by miRNA-sensing guide RNAs.
Nucleic acid nanostructures offer unique opportunities for biomedical applications due to their sequence-programmable structures and functions, which enable the design of complex responses to molecular cues. Control of the biological activity of therapeutic cargoes based on endogenous molecular signatu…
Progress and prospects in antisense oligonucleotide-mediated exon skipping therapies for Duchenne muscular dystrophy.
Recent years have seen enormous progress in the field of advanced therapeutics for the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). In particular, four antisense oligonucleotide (ASO) therapies targeting various DMD-causing mutations have achieved FDA approval, marking major…
Urine-derived stem cells serve as a robust platform for generating native or engineered extracellular vesicles.
BACKGROUND: Mesenchymal stromal cell (MSC) therapy holds great potential yet efficacy and safety concerns with cell therapy persist. The beneficial effects of MSCs are often attributed to their secretome that includes extracellular vesicles (EVs). EVs carry biologically active molecules, protected by a lipid bilayer…