Delivery of modified mRNA encoding vesicular stomatitis virus matrix protein for colon cancer gene therapy

Men, Ke; Zhang, Rui; Zhang, Xueyan; Huang, Rong; Zhu, Guonian; Tong, Rongsheng; Yang, Li; Wei, Yuquan; Duan, Xingmei

doi:10.1039/c7ra13656k

Cited by 13 publications

(13 citation statements)

References 49 publications

(59 reference statements)

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“…Also, the particle size, net surface charge, and nonaggregability of particles in the medium, including a highly efficient endocytosis and intracellular release, are also contributed for a higher gene knockdown, efficiency as described earlier. ,,,, A combination of PS–lipid nanoparticles exhibited a higher gene knockdown efficiency with a better delivery of dsRNA in Sf9 cells when compared to hydroxyapatite nanoparticles, guanidinium-functionalized complex, and chitosan nanoparticles. Moreover, PS–lipid nanoparticles were also reported to achieve a higher knockdown efficiency in different mammalian cell lines. ,,, These data suggest that a combination of PS–lipid nanoparticles protected dsRNA and enhanced its cellular uptake, endosomal escape, and release into cytoplasm resulting in an improved RNAi.…”

Section: Resultsmentioning

confidence: 88%

Protamine–Lipid–dsRNA Nanoparticles Improve RNAi Efficiency in the Fall Armyworm, Spodoptera frugiperda

Dhandapani

Gurusamy

Palli

2022

J. Agric. Food Chem.

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Developing safe and effective double-stranded RNA (dsRNA) delivery systems remains a major challenge for gene silencing, especially in lepidopteran insects. This study evaluated the protamine sulfate (PS)/lipid/dsRNA nanoparticle (NP) delivery system for RNA interference (RNAi) in cells and larvae of the fall armyworm (FAW), Spodoptera frugiperda, a major worldwide pest. A highly efficient gene delivery formulation was prepared using a cationic biopolymer, PS, and a cationic lipid, Cellfectin (CF), complexed with dsRNA. The NPs were prepared by a two-step self-assembly method. The formation of NPs was revealed by dynamic light scattering and transmission electron microscopy. The formation of CF/dsRNA/PS NPs was spherical in shape and size, ranging from 20 to 100 nm with a positive charge (+23.3 mV). Interestingly, prepared CF/dsRNA/PS NPs could protect dsRNA (95%) from nuclease degradation and thus significantly improve the stability of dsRNA. Formulations prepared by combining EGFP DNA with CF/PS increased transfection efficiency in Sf9 cells compared to PS/EGFP and CF/EGFP NPs. Also, the PS/CF/dsRNA NPs enhanced the endosomal escape for the intracellular delivery of dsRNA. The gene knockdown efficiency was assessed in Sf9 Luciferase (Luc) stable cells after a 72 h incubation with CF/dsRNA/PS, PS/dsRNA, CF/dsRNA, or naked dsRNA. Knockdown of the Luc gene was detected in CF/dsRNA/PS (76%) and PS/dsRNA (42.4%) not CF/dsRNA (19.5%) and naked dsRNA (10.3%) in Sf9 Luc cells. Moreover, CF/dsIAP/PS (25 μg of dsRNA targeting the inhibitor of apoptosis, IAP, gene of FAW) NPs showed knockdown of the IAP gene (39.5%) and mortality (55%) in FAW larvae. These results highlight the potential application of PS/lipid/dsRNA NPs for RNA-mediated control of insect pests.

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Section: Resultsmentioning

confidence: 88%

Protamine–Lipid–dsRNA Nanoparticles Improve RNAi Efficiency in the Fall Armyworm, Spodoptera frugiperda

Dhandapani

Gurusamy

Palli

2022

J. Agric. Food Chem.

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“…These modified T cells can identify specific tumor cells and kill them. So far, the mRNA-based cancer immunotherapy has been tried to cure many cancers, such as glioblastoma [178] , leukemia [179] , colon cancer [ 180 , 181 ], renal cell cancer [182] , and melanoma [176] . Typical examples of mRNA-based cancer immunotherapy are shown in Table 1 .…”

Section: Therapeutic Applicationsmentioning

confidence: 99%

Synthetic modified messenger RNA for therapeutic applications

et al. 2021

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Synthetic modified messenger RNA (mRNA) has manifested great potentials for therapeutic applications such as vaccines and gene therapies, with the recent mRNA vaccines for global pandemic COVID-19 (corona virus disease 2019) attracting the tremendous attention. The chemical modifications and delivery vehicles of synthetic mRNAs are the two key factors for their in vivo therapeutic applications. Chemical modifications like nucleoside methylation endow the synthetic mRNAs with high stability and reduced stimulation of innate immunity. The development of scalable production of synthetic mRNA and efficient mRNA formulation and delivery strategies in recent years have remarkably advanced the field. It is worth noticing that we had limited knowledge on the roles of mRNA modifications in the past. However, the last decade has witnessed not only new discoveries of several naturally occurring mRNA modifications but also substantial advances in understanding their roles on regulating gene expression. It is highly necessary to reconsider the therapeutic system made by synthetic modified mRNAs and delivery vectors. In this review, we will mainly discuss the roles of various chemical modifications on synthetic mRNAs, briefly summarize the progresses of mRNA delivery strategies, and highlight some latest mRNA therapeutics applications including infectious disease vaccines, cancer immunotherapy, mRNA-based genetic reprogramming and protein replacement, mRNA-based gene editing.

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“…As a type of polymer copolymer, possessing biodegradability and biocompatibility, PEG/PCL copolymers show promising applications in drug delivery systems [11–13]. Based on MPEG-PCL micelles, we used amphiphilic DOTAP to modify MPEG-PCL copolymer in one step, creating the cationic self-assembled DOTAP and MPEG-PCL hybrid micelles (DMP) [14–17]. These micelles show a promising prospect in the delivery of chemical drugs and gene drugs with excellent stability and safety.…”

Section: Introductionmentioning

confidence: 99%

Cationic micelle-based siRNA delivery for efficient colon cancer gene therapy

Zhong

Jiang

et al. 2019

Nanoscale Res Lett

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Small interfering RNA (siRNA)-based gene therapy has provided an alternative strategy for cancer therapy. One of the key components within gene therapy process is the delivery system. As a novel non-viral gene vector, DMP, prepared by modifying mPEG-PCL micelle with cationic DOTAP lipid, has been prepared and successfully applied in plasmid DNA-based colon cancer gene therapy study. However, its potential in siRNA delivery is unknown. In this study, the preparation process of DMP was optimized and the anti-cancer efficacies of the DMP/siMcl1 and DMP/siBcl-xl complexes were studied on a mouse colon cancer model. Our results demonstrated that DMP cationic micelle-delivered siRNAs could effectively inhibit the growth of C26 colon cancer cells in vitro . Meanwhile, intratumoral administration of DMP/siMcl1 and DMP/siBcl-xl complexes obviously suppressed subcutaneous tumor model in vivo. These results suggest the DMP/siRNA complex to be a potential candidate for cancer gene therapy.

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Delivery of modified mRNA encoding vesicular stomatitis virus matrix protein for colon cancer gene therapy

Cited by 13 publications

References 49 publications

Protamine–Lipid–dsRNA Nanoparticles Improve RNAi Efficiency in the Fall Armyworm, Spodoptera frugiperda

Protamine–Lipid–dsRNA Nanoparticles Improve RNAi Efficiency in the Fall Armyworm, Spodoptera frugiperda

Synthetic modified messenger RNA for therapeutic applications

Cationic micelle-based siRNA delivery for efficient colon cancer gene therapy

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