Author Correction: Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation

Yang, Zhaogang; Shi, Junfeng; Xie, Jing; Wang, Yifan; Sun, Jingyao; Liu, Tongzheng; Zhao, Yarong; Zhao, Xiuting; Wang, Xinmei; Ma, Yifan; Malkoc, Veysi; Chiang, Chi‐Ling; Deng, Weiye; Chen, Yuanxin; Fu, Yuan; Kwak, Kwang Joo; Fan, Yamin; Chen, Kang; Yin, Chang-Cheng; Rhee, June; Bertani, Paul; Otero, José; Lu, Wu; Yun, Kyuson; Lee, Andrew S.; Jiang, Wen; Teng, Lesheng; Kim, Betty Y.S.; Lee, L. James

doi:10.1038/s41551-021-00725-w

Cited by 8 publications

(4 citation statements)

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“…Recent studies reported the efficacy of exosome-mediated delivery of siRNAs in different cancers such as breast cancer [ 145 ], leukemia [ 146 ] and glioma [ 147 ].…”

Section: Introductionmentioning

confidence: 99%

Novel approaches in cancer treatment: preclinical and clinical development of small non-coding RNA therapeutics

Cuciniello

Filosa

Crispi

2021

J Exp Clin Cancer Res

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Short or small interfering RNAs (siRNAs) and microRNA (miRNAs) are molecules similar in size and function able to inhibit gene expression based on their complementarity with mRNA sequences, inducing the degradation of the transcript or the inhibition of their translation.siRNAs bind specifically to a single gene location by sequence complementarity and regulate gene expression by specifically targeting transcription units via posttranscriptional gene silencing. miRNAs can regulate the expression of different gene targets through their imperfect base pairing.This process - known as RNA interference (RNAi) - modulates transcription in order to maintain a correct physiological environment, playing a role in almost the totality of the cellular pathways.siRNAs have been evolutionary evolved for the protection of genome integrity in response to exogenous and invasive nucleic acids such as transgenes or transposons. Artificial siRNAs are widely used in molecular biology for transient silencing of genes of interest. This strategy allows to inhibit the expression of any target protein of known sequence and is currently used for the treatment of different human diseases including cancer.Modifications and rearrangements in gene regions encoding for miRNAs have been found in cancer cells, and specific miRNA expression profiles characterize the developmental lineage and the differentiation state of the tumor. miRNAs with different expression patterns in tumors have been reported as oncogenes (oncomirs) or tumor-suppressors (anti-oncomirs). RNA modulation has become important in cancer research not only for development of early and easy diagnosis tools but also as a promising novel therapeutic approach.Despite the emerging discoveries supporting the role of miRNAs in carcinogenesis and their and siRNAs possible use in therapy, a series of concerns regarding their development, delivery and side effects have arisen.In this review we report the biology of miRNAs and siRNAs in relation to cancer summarizing the recent methods described to use them as novel therapeutic drugs and methods to specifically deliver them to cancer cells and overcome the limitations in the use of these molecules.

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“…Recent studies reported the efficacy of exosome-mediated delivery of siRNAs in different cancers such as breast cancer [ 145 ], leukemia [ 146 ] and glioma [ 147 ].…”

Section: Introductionmentioning

confidence: 99%

Novel approaches in cancer treatment: preclinical and clinical development of small non-coding RNA therapeutics

Cuciniello

Filosa

Crispi

2021

J Exp Clin Cancer Res

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“…Transport of specific genes by sEVs can also compensate for defects in these genes. The delivery of specific mRNA molecules has been shown to restore the expression of phosphatase and tensin homologue (PTEN) in PTEN-deficient mice with glioma, leading to enhanced inhibition of tumour growth and increased survival [ 226 ].…”

Section: Naïve or Engineered Sevs As Immune Vaccination Or As Carrier...mentioning

confidence: 99%

The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy

Qian

et al. 2022

J Exp Clin Cancer Res

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Extracellular vesicles (EVs) facilitate the extracellular transfer of proteins, lipids, and nucleic acids and mediate intercellular communication among multiple cells in the tumour environment. Small extracellular vesicles (sEVs) are defined as EVs range in diameter from approximately 50 to 150 nm. Tumour-derived sEVs (TDsEVs) and immune cell-derived sEVs have significant immunological activities and participate in cancer progression and immune responses. Cancer-specific molecules have been identified on TDsEVs and can function as biomarkers for cancer diagnosis and prognosis, as well as allergens for TDsEVs-based vaccination. Various monocytes, including but not limited to dendritic cells (DCs), B cells, T cells, natural killer (NK) cells, macrophages, and myeloid-derived suppressor cells (MDSCs), secrete sEVs that regulate immune responses in the complex immune network with either protumour or antitumour effects. After engineered modification, sEVs from immune cells and other donor cells can provide improved targeting and biological effects. Combined with their naïve characteristics, these engineered sEVs hold great potential as drug carriers. When used in a variety of cancer therapies, they can adjunctly enhance the safety and antitumor efficacy of multiple therapeutics. In summary, both naïve sEVs in the tumour environment and engineered sEVs with effector cargoes are regarded as showing promising potential for use in cancer diagnostics and therapeutics.

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“…Based on the fact that CD47 is expressed on the membrane of exosomes, 30 the target gene could be designed to be expressed at the surface of exosomes. 31 Using the exosome carrier, the oligonucleotide drug (miRNA-29b-2) is targeted to the hippocampus memory area of the brain for the treatment of AD.…”

Section: Introductionmentioning

confidence: 99%

Engineered Exosomes Containing microRNA-29b-2 and Targeting the Somatostatin Receptor Reduce Presenilin 1 Expression and Decrease the β-Amyloid Accumulation in the Brains of Mice with Alzheimer’s Disease

Lin,

Hsu,

et al. 2024

IJN

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Exosomes are membrane vesicles secreted by various cells and play a crucial role in intercellular communication. They can be excellent delivery vehicles for oligonucleotide drugs, such as microRNAs, due to their high biocompatibility. MicroRNAs have been shown to be more stable when incorporated into exosomes; however, the lack of targeting and immune evasion is still the obstacle to the use of these microRNA-containing nanocarriers in clinical settings. Our goal was to produce functional exosomes loaded with target ligands, immune evasion ligand, and oligonucleotide drug through genetic engineering in order to achieve more precise medical effects. Methods: To address the problem, we designed engineered exosomes with exogenous cholecystokinin (CCK) or somatostatin (SST) as the targeting ligand to direct the exosomes to the brain, as well as transduced CD47 proteins to reduce the elimination or phagocytosis of the targeted exosomes. MicroRNA-29b-2 was the tested oligonucleotide drug for delivery because our previous research showed that this type of microRNA was capable of reducing presenilin 1 (PSEN1) gene expression and decreasing the βamyloid accumulation for Alzheimer's disease (AD) in vitro and in vivo. Results: The engineered exosomes, containing miR29b-2 and expressing SST and CD47, were produced by gene-modified dendritic cells and used in the subsequent experiments. In comparison with CD47-CCK exosomes, CD47-SST exosomes showed a more significant increase in delivery efficiency. In addition, CD47-SST exosomes led to a higher delivery level of exosomes to the brains of nude mice when administered intravenously. Moreover, it was found that the miR29b-2-loaded CD47-SST exosomes could effectively reduce PSEN1 in translational levels, which resulted in an inhibition of beta-amyloid oligomers production both in the cell model and in the 3xTg-AD animal model. Conclusion:Our results demonstrated the feasibility of the designed engineered exosomes. The application of this exosomal nanocarrier platform can be extended to the delivery of other oligonucleotide drugs to specific tissues for the treatment of diseases while evading the immune system.

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Author Correction: Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation

Cited by 8 publications

References 0 publications

Novel approaches in cancer treatment: preclinical and clinical development of small non-coding RNA therapeutics

Novel approaches in cancer treatment: preclinical and clinical development of small non-coding RNA therapeutics

The roles of small extracellular vesicles in cancer and immune regulation and translational potential in cancer therapy

Engineered Exosomes Containing microRNA-29b-2 and Targeting the Somatostatin Receptor Reduce Presenilin 1 Expression and Decrease the β-Amyloid Accumulation in the Brains of Mice with Alzheimer’s Disease

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