Efficient RNA drug delivery using red blood cell extracellular vesicles

Usman, Waqas Muhammad; Pham, Tin Chanh; Kwok, Yuk Yan; Vu, Luyen Tien; Ma, Victor; Peng, Boya; Chan, Yuen San; Wei, Likun; Chin, Siew Mei; Azad, Ajijur; He, Bai-Liang; Leung, Anskar Yu Hung; Yang, Mian; Shyh‐Chang, Ng; Cho, William C.; Shi, Jiahai; Le, Minh Vuong

doi:10.1038/s41467-018-04791-8

Cited by 459 publications

(487 citation statements)

References 35 publications

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“…Importantly, we used donor cells stably expressing Cre, allowing us to study only cell-derived vesicle-mediated transfer of Cre cytosolic RNA (functional RNA) and protein, without the interference of lipid-based carriers that may end up in NVs/EVs and affect their behavior. [36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Biofabrication of Cell-Derived Nanovesicles: A Potential Alternative to Extracellular Vesicles for Regenerative Medicine

Ilahibaks

Lei

Mol

et al. 2019

Cells

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Extracellular vesicles (EVs) are mediators of intercellular communication by transferring functional biomolecules from their originating cells to recipient cells. This intrinsic ability has gained EVs increased scientific interest in their use as a direct therapeutic in the field of regenerative medicine or as vehicles for drug delivery. EVs derived from stem cells or progenitor cells can act as paracrine mediators to promote repair and regeneration of damaged tissues. Despite substantial research efforts into EVs for various applications, their use remains limited by the lack of highly efficient and scalable production methods. Here, we present the biofabrication of cell-derived nanovesicles (NVs) as a scalable, efficient, and cost-effective production alternative to EVs. We demonstrate that NVs have a comparable size and morphology as EVs, but lack standard EV (surface) markers. Additionally, in vitro uptake experiments show that human fetal cardiac fibroblast, endothelial cells, and cardiomyocyte progenitor cells internalize NVs. We observed that cardiac progenitor cell-derived NVs and EVs are capable of activating mitogen-activated protein kinase 1/2 (MAPK1/2)-extracellular signal-regulated kinase, and that both NVs and EVs derived from A431 and HEK293 cells can functionally deliver Cre-recombinase mRNA or protein to other cells. These observations indicate that NVs may have similar functional properties as EVs. Therefore, NVs have the potential to be applied for therapeutic delivery and regenerative medicine purposes.

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Section: Discussionmentioning

confidence: 99%

Biofabrication of Cell-Derived Nanovesicles: A Potential Alternative to Extracellular Vesicles for Regenerative Medicine

Ilahibaks

Lei

Mol

et al. 2019

Cells

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“…In addition, CD47 on RBC-derived EVs is capable of interacting with its receptor signal regulatory protein alpha (SIRPa) on macrophages to protect RBCs-derived EVs from clearance by initiating the 'don't eat me' signal (Tian et al, 2014). Usman et al (2018) have described a strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA delivery by RBC-derived EVs showed highly robust gene inhibition and CRISPR-Cas9 genome editing in vitro and vivo with no observable cytotoxicity (Usman et al, 2018).…”

Section: Othersmentioning

confidence: 99%

“…Usman et al (2018) have described a strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA delivery by RBC-derived EVs showed highly robust gene inhibition and CRISPR-Cas9 genome editing in vitro and vivo with no observable cytotoxicity (Usman et al, 2018).…”

Section: Othersmentioning

confidence: 99%

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

et al. 2020

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Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane vesicles derived from most cell types. Carrying diverse biomolecules from their parent cells, EVs are important mediators of intercellular communication and thus play significant roles in physiological and pathological processes. Owing to their natural biogenesis process, EVs are generated with high biocompatibility, enhanced stability, and limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic delivery vehicles. EVs have been reported to be used for the delivery of siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, and CRISPR/Cas9 in the treatment of various diseases. As a natural drug delivery vectors, EVs can penetrate into the tissues and be bioengineered to enhance the targetability. Although EVs' characteristics make them ideal for drug delivery, EV-based drug delivery remains challenging, due to lack of standardized isolation and purification methods, limited drug loading efficiency, and insufficient clinical grade production. In this review, we summarized the current knowledge on the application of EVs as DDS from the perspective of different cell origin and weighted the advantages and bottlenecks of EV-based DDS. ARTICLE HISTORY

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“…Exosomes may also be used to solve a number of the issues surrounding currently used drug therapy methods, which involve programmable RNA, which has low uptake efficiency, is highly cytotoxic and is thus unsuitable for clinical practice (108). Researchers have proposed and verified the effectiveness of a new strategy for the generation of large amounts of RBC-derived EVs for delivering RNA drugs (109). The use of gold nanoparticle targeting approaches to generate specific types of exosomes offers an alternative for the selective, targeted elimination of cancer cells (110).…”

Section: Exosomal Circrnas Promote the Generation Of Premeta-mentioning

confidence: 99%

“…The use of gold nanoparticle targeting approaches to generate specific types of exosomes offers an alternative for the selective, targeted elimination of cancer cells (110). In summary, exosomes are vesicles that can be artificially engineered into useful treatment vectors as a therapeutic agent against cancer (13,109,111,112).…”

Section: Exosomal Circrnas Promote the Generation Of Premeta-mentioning

confidence: 99%

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

et al. 2020

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Exosomes are nanoscale phospholipid bilayer vesicles that can be artificially engineered into vectors for the treatment of cancer. Circular RNA (circRNA), a type of non-coding RNA, has crucial regulatory functions in various aspects of cancer, such as tumorigenesis, apoptosis, proliferation, invasion, metastasis and chemo-and radiotherapeutic resistance, as well as in cancer prognosis. Notably, the exosomal transfer of circRNAs may function to both promote and inhibit cancer. Numerous studies have addressed the importance of circRNAs in cancer and non-coding RNAs (such as microRNAs and long non-coding RNAs) in exosomes. However, little research has focussed on a class of RNAs called exosomal circRNAs. The present review discusses current studies regarding exosomal circRNAs, including their biogenesis and biological functions, their abundance in exosomes and possible sorting mechanisms and their potential roles in both promoting and inhibiting cancer. It is predicted that in the next five years there will be increasing research exploring the functional mechanisms of exosomal circRNA in various diseases, in particular their roles in cancer genesis and progression.

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Efficient RNA drug delivery using red blood cell extracellular vesicles

Cited by 459 publications

References 35 publications

Biofabrication of Cell-Derived Nanovesicles: A Potential Alternative to Extracellular Vesicles for Regenerative Medicine

Biofabrication of Cell-Derived Nanovesicles: A Potential Alternative to Extracellular Vesicles for Regenerative Medicine

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

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