Extracellular vesicles induce minimal hepatotoxicity and immunogenicity

Saleh, Amer F.; Lázaro-Ibáñez, Elisa; Forsgard, Malin; Shatnyeva, Olga; Osteikoetxea, Xabier; Karlsson, Fredrik; Heath, Nikki; Ingelsten, Madeleine; Rose, Jonathan A.; Harris, Jayne; Mairesse, Maelle; Bates, Stephanie M.; Clausen, Maryam; Etal, Damla; Leonard, Emilyanne; Fellows, Mick D.; Dekker, Niek; Edmunds, Nick

doi:10.1039/c8nr08720b

Cited by 136 publications

(130 citation statements)

References 46 publications

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“…In addition, the use of exosomes would avoid various issues related to cell therapy such as the inability to sterilize the cells, short shelf-life, and limited quality control (QC) before release [41,44]. A couple of studies have also reported that exosomes from MSCs and HEK 293T did not cause toxicity in vivo or in vitro [44][45][46][47][48]. A recent study suggested that long-term repetitive injection of exosomes does not induce toxicity [45].…”

Section: Exosomes and Extracellular Vesiclesmentioning

confidence: 99%

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Yi¹,

Lee²,

Kim

et al. 2020

IJMS

141

131

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Exosomes are nano-sized membranous vesicles produced by nearly all types of cells. Since exosome-like vesicles are produced in an evolutionarily conserved manner for information and function transfer from the originating cells to recipient cells, an increasing number of studies have focused on their application as therapeutic agents, drug delivery vehicles, and diagnostic targets. Analysis of the in vivo distribution of exosomes is a prerequisite for the development of exosome-based therapeutics and drug delivery vehicles with accurate prediction of therapeutic dose and potential side effects. Various attempts to evaluate the biodistribution of exosomes obtained from different sources have been reported. In this review, we examined the current trends and the advantages and disadvantages of the methods used to determine the biodistribution of exosomes by molecular imaging. We also reviewed 29 publications to compare the methods employed to isolate, analyze, and label exosomes as well as to determine the biodistribution of labeled exosomes.

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Section: Exosomes and Extracellular Vesiclesmentioning

confidence: 99%

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Yi¹,

Lee²,

Kim

et al. 2020

IJMS

141

131

View full text Add to dashboard Cite

show abstract

“…The most promising delivery system for CRISPR epi-editors with prolonged expression is AAV (adeno-associated virus) vectors with a packaging capacity of 5 kb [50]. In spite the size of the SpCas9-gRNA-effector (Streptococcus pyogenes Cas9) complex exceeds an average packaging limit, the effective in vivo delivery is achievable with smaller dCas9 variants, or a different, less immunogenic delivery systems, such as EVs (extracellular vesicles), carrying CRISPR epi-editor plasmids or viral vectors [50][51][52][53][54]. Achieving the efficient delivery, high specificity, and non-immunogenicity represent the most crucial challenges standing before epigenome editing [55].…”

Section: Crispr-based Epigenome Editors (Crispr Epi-editors)mentioning

confidence: 99%

CRISPR/Cas9 Epigenome Editing Potential for Rare Imprinting Diseases: A Review

Syding

Nickl

Kašpárek

et al. 2020

Cells

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Imprinting diseases (IDs) are rare congenital disorders caused by aberrant dosages of imprinted genes. Rare IDs are comprised by a group of several distinct disorders that share a great deal of homology in terms of genetic etiologies and symptoms. Disruption of genetic or epigenetic mechanisms can cause issues with regulating the expression of imprinted genes, thus leading to disease. Genetic mutations affect the imprinted genes, duplications, deletions, and uniparental disomy (UPD) are reoccurring phenomena causing imprinting diseases. Epigenetic alterations on methylation marks in imprinting control centers (ICRs) also alters the expression patterns and the majority of patients with rare IDs carries intact but either silenced or overexpressed imprinted genes. Canonical CRISPR/Cas9 editing relying on double-stranded DNA break repair has little to offer in terms of therapeutics for rare IDs. Instead CRISPR/Cas9 can be used in a more sophisticated way by targeting the epigenome. Catalytically dead Cas9 (dCas9) tethered with effector enzymes such as DNA de- and methyltransferases and histone code editors in addition to systems such as CRISPRa and CRISPRi have been shown to have high epigenome editing efficiency in eukaryotic cells. This new era of CRISPR epigenome editors could arguably be a game-changer for curing and treating rare IDs by refined activation and silencing of disturbed imprinted gene expression. This review describes major CRISPR-based epigenome editors and points out their potential use in research and therapy of rare imprinting diseases.

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“…Interestingly, it has been shown that the composition of extracellular vesicles can be modified by engineering either the producing cells or the vesicles after isolation. Although EVs are considered poorly immunogenic carriers (Saleh et al, 2019), they play a role in mediating immunostimulating or immunosuppressive responses (Robbins and Morelli, 2014).…”

Section: Extracellular Vesicles (Evs)mentioning

confidence: 99%

Engineering Targeting Materials for Therapeutic Cancer Vaccines

Briquez

Hauert

Titta³

et al. 2020

Front. Bioeng. Biotechnol.

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Therapeutic cancer vaccines constitute a valuable tool to educate the immune system to fight tumors and prevent cancer relapse. Nevertheless, the number of cancer vaccines in the clinic remains very limited to date, highlighting the need for further technology development. Recently, cancer vaccines have been improved by the use of materials, which can strongly enhance their intrinsic properties and biodistribution profile. Moreover, vaccine efficacy and safety can be substantially modulated through selection of the site at which they are delivered, which fosters the engineering of materials capable of targeting cancer vaccines to specific relevant sites, such as within the tumor or within lymphoid organs, to further optimize their immunotherapeutic effects. In this review, we aim to give the reader an overview of principles and current strategies to engineer therapeutic cancer vaccines, with a particular focus on the use of sitespecific targeting materials. We will first recall the goal of therapeutic cancer vaccination and the type of immune responses sought upon vaccination, before detailing key components of cancer vaccines. We will then present how materials can be engineered to enhance the vaccine's pharmacokinetic and pharmacodynamic properties. Finally, we will discuss the rationale for site-specific targeting of cancer vaccines and provide examples of current targeting technologies.

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Extracellular vesicles induce minimal hepatotoxicity and immunogenicity

Abstract: The absence of any significant toxicity associated with EVs in vitro and in vivo support the prospective use of EVs for therapeutic applications and for drug delivery.

Cited by 136 publications

References 46 publications

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

Advances in Analysis of Biodistribution of Exosomes by Molecular Imaging

CRISPR/Cas9 Epigenome Editing Potential for Rare Imprinting Diseases: A Review

Engineering Targeting Materials for Therapeutic Cancer Vaccines

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