Novel Endogenous Engineering Platform for Robust Loading and Delivery of Functional mRNA by Extracellular Vesicles DOI Open Access
Antje M. Zickler, Xiuming Liang, Dhanu Gupta

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 20, 2023

ABSTRACT Messenger RNA (mRNA) has emerged as an attractive therapeutic molecule for a plethora of clinical applications. For in vivo functionality, mRNA therapeutics require encapsulation into effective, stable, and safe delivery systems to protect the cargo from degradation reduce immunogenicity. Here, bioengineering platform efficient loading functional using bionormal nanoparticles, Extracellular Vesicles (EVs), is established by expressing highly specific RNA-binding domain fused CD63 EV producer cells stably target mRNA. The additional combination with fusogenic endosomal escape moiety, VSVg, enables at doses substantially lower than currently used clinically synthetic lipid-based nanoparticles. Importantly, application EVs loaded effective cancer immunotherapy proves aggressive melanoma mouse model. This technology addresses substantial drawbacks associated EV-based nucleic acid leap forward Graphical Abstract (Figure created BioRender)

Language: Английский

Tailored apoptotic vesicles promote bone regeneration by releasing the osteoinductive brake DOI Creative Commons
Yawen Cheng, Yuan Zhu,

Yaoshan Liu

et al.

International Journal of Oral Science, Journal Year: 2024, Volume and Issue: 16(1)

Published: April 16, 2024

Abstract Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs other extracellular (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize osteoinduction activity, it necessary determine the unique cargo profiles MSC-apoVs. We previously established protein landscape identified specific However, features functions miRNAs in unclear. In this study, we MSCs, MSC-apoVs, MSC-exosomes two types MSC. generated a map seven specifically MSC-exosomes, which classified apoV-specific miRNAs. Among these miRNAs, hsa-miR-4485-3p was most abundant stable. Next, explored its function apoV-mediated osteoinduction. Unexpectedly, inhibited osteogenesis promoted adipogenesis by targeting AKT pathway. Tailored apoVs with downregulated exhibited greater on regeneration than control apoVs. Like releasing brake, acquired more powerful summary, miRNA cargos, including tailored high promising apoV-based therapies regeneration.

Language: Английский

Citations

4
Extracellular Vesicle Spherical Nucleic Acids DOI Creative Commons
Hao Chen,

Qiaojiao Ding,

Lin Li

et al.

JACS Au, Journal Year: 2024, Volume and Issue: 4(6), P. 2381 - 2392

Published: May 30, 2024

Extracellular vesicles (EVs) are naturally occurring secreted by cells that can transport cargo between cells, making them promising bioactive nanomaterials. However, due to the complex and heterogeneous biological characteristics, a method for robust EV manipulation efficient delivery is still lacking. Here, we developed novel class of extracellular vesicle spherical nucleic acid (EV-SNA) nanostructures with scalability, programmability, cellular delivery. EV-SNA was constructed through simple hydrophobic coassembly natural EVs cholesterol-modified oligonucleotides be stable 1 month at room temperature. Based on programmable shells, respond AND logic gates achieve assembly manipulation. Importantly, from wide range sources EV, enhancing capability nearly 10–20 times. Compared artificial liposomal SNA, endogenous exhibited better biocompatibility more effective antisense in hard-to-transfect primary stem cells. Additionally, deliver functional immune regulation. As material form, may provide modular framework paradigm EV-based applications drug delivery, disease treatment, nanovaccines, other fields.

Language: Английский

Citations

4
Cell dehydration enables massive production of engineered membrane vesicles with therapeutic functions DOI Creative Commons

Jie Liu,

Tingting Shen, Yu Zhang

et al.

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(7)

Published: July 1, 2024

Abstract Extracellular vesicles (EVs) have emerged as promising biomaterials for the treatment of different disease. However, only handful types EVs with clinical transformation potential been reported to date, and their preparation on a large scale under biosafety‐controlled conditions is limited. In this study, we characterize novel type EV application potential: dehydration‐induced extracellular (DIMVs). DIMV micron‐diameter cell vesicle that contains more bioactive molecules, such proteins RNA, but not DNA, than previously vesicles. The extraordinarily straightforward, which possesses high level biosafety, protein utilization ratio roughly 600 times greater naturally secreted EVs. Additional experiments demonstrate viability pre‐ or post‐isolation modification, including gene editing, nucleic acid encapsulation surface anchoring, size adjustment. Finally, animal models, directly show biosafety immunogenicity DIMV, investigate its tumour vaccine drug carrier in cancer treatment.

Language: Английский

Citations

4
Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids DOI Creative Commons

Johannes Bader,

Finn Brigger,

Jean‐Christophe Leroux

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 115461 - 115461

Published: Oct. 1, 2024

Language: Английский

Citations

4
Extracellular Vesicles as Tools for Crossing the Blood–Brain Barrier to Treat Lysosomal Storage Diseases DOI Creative Commons

Giovanni Lerussi,

Verónica Villagrasa-Araya,

Marc Moltó‐Abad

et al.

Life, Journal Year: 2025, Volume and Issue: 15(1), P. 70 - 70

Published: Jan. 9, 2025

Extracellular vesicles (EVs) are nanosized, membrane-bound structures that have emerged as promising tools for drug delivery, especially in the treatment of lysosomal storage disorders (LSDs) with central nervous system (CNS) involvement. This review highlights unique properties EVs, such their biocompatibility, capacity to cross blood-brain barrier (BBB), and potential therapeutic cargo loading, including enzymes genetic material. Current therapies LSDs, like enzyme replacement therapy (ERT), often fail address neurological symptoms due inability BBB. EVs offer a viable alternative, allowing targeted delivery CNS improving outcomes. We discuss recent advancements engineering modification enhance targeting, circulation time stability, provide detailed overview application Gaucher Fabry diseases, Sanfilippo syndrome. Despite potential, challenges remain scaling production, ensuring isolation purity, meeting regulatory requirements. Future developments will focus on overcoming these barriers, paving way clinical translation EV-based LSDs other disorders.

Language: Английский

Citations

0
Harnessing hydrodynamics for high-yield production of extracellular vesicles from stem cells spheroids with specific cargo profiling DOI
Solène Lenoir, Elliot Thouvenot,

Giacomo Gropplero

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

ABSTRACT This study presents a novel method and device for the hydrodynamic production of extracellular vesicles (EVs) derived from biomimetic multicellular 3D spheroids, enabling high-throughput particle release that is 10 to 20 times higher than in non-stimulated conditions. The facilitates formation spheroids human mesenchymal stem cells (hMSCs), offering an all-in-one approach both spheroid generation EV release. Production are reduced just few hours, with yield further increased by alternating periods high flow recovery sequential approach. Using this system, we explored impact starvation conditions on protein cargo EVs, identifying distinct markers through proteomics. Specifically, stimulation enriched EVs plasma membrane-derived mitochondrial proteins, revealing divergent biogenesis pathways. Importantly, produced exhibited therapeutic properties, demonstrated effects wound healing, angiogenesis, anti-inflammatory responses, some showing enhanced efficacy under stimulation.

Language: Английский

Citations

0
CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis DOI
Sunyoung Park,

Yeo‐Jun Yoon,

Yong-Pyo Hong

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 47, P. 229 - 247

Published: Jan. 24, 2025

Language: Английский

Citations

0
Developing anti-TDE vaccine for sensitizing cancer cells to treatment and metastasis control DOI Creative Commons
Stephene S. Meena,

Benson Kiprono Kosgei,

Geofrey F. Soko

et al.

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 27, 2025

Tumor-derived exosomes (TDEs) mediate oncogenic communication, which modifies target cells to reinforce a tumor-promoting microenvironment. TDEs support cancer progression by suppressing anti-tumor immune responses, promoting metastasis, and conferring drug resistance. Thus, targeting could improve the efficacy of anti-cancer treatments control metastasis. Current strategies inhibit TDE-mediated communication including drug-based genetic modification-based inhibition TDE release and/or uptake, have proved be inefficient. In this work, we propose surface engineering express foreign antigens that will trigger life-long anti-TDE responses. The possibility combining vaccines with other such as chemotherapy, radiotherapy, targeted therapy, surgery is also explored.

Language: Английский

Citations

0
Engineered Immunomodulatory Extracellular Vesicles from Epithelial Cells with the Capacity for Stimulation of Innate and Adaptive Immunity in Cancer and Autoimmunity DOI
Xin Luo, Fernanda G. Kugeratski, Dara P. Dowlatshahi

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Extracellular vesicles (EVs) are generated in all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells has been shown to be safe, despite carrying an array functional molecules, including thousands proteins. To address whether cell-derived can modified acquire the capacity induce immune response, we engineered 293T harbor immunomodulatory molecules CD80, OX40L, PD-L1. We demonstrated abundant levels these proteins EVs. Functionally, efficiently elicited positive negative costimulation human murine T In setting cancer autoimmune hepatitis, modulated cell functions altered disease progression. OX40L also provided enhanced antitumor activity combination with anti-CTLA-4 melanoma-bearing mice. addition, added multiple (EVmIM), attempting elicit response both lymphoid myeloid compartments. The EVmIM containing 4-1BBL, CD40L, CD2, CD32 engaged antigen presenting (APCs) melanoma tumors, demonstrating for activity. Our work provides evidence that specific responses translational potential modulate pathological settings.

Language: Английский

Citations

0
Differential protein and mRNA cargo loading into engineered large and small extracellular vesicles reveals differences in in vitro and in vivo assays DOI

Zuriñe Erana-Perez,

Manoli Igartúa, Edorta Santos‐Vizcaíno

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 951 - 966

Published: Feb. 3, 2025

Language: Английский

Citations

0