Dataset Information

Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs.

ABSTRACT: Targeted delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system to the receptor cells is essential for in vivo gene editing. Exosomes are intensively studied as a promising targeted drug delivery carrier recently, while limited by their low efficiency in encapsulating of large nucleic acids. Here, a kind of hybrid exosomes with liposomes is developed via simple incubation. Different from the original exosomes, the resultant hybrid nanoparticles efficiently encapsulate large plasmids, including the CRISPR-Cas9 expression vectors, similarly as the liposomes. Moreover, the resultant hybrid nanoparticles can be endocytosed by and express the encapsulated genes in the mesenchymal stem cells (MSCs), which cannot be transfected by the liposome alone. Taken together, the exosome-liposome hybrid nanoparticles can deliver CRISPR-Cas9 system in MSCs and thus be promising in in vivo gene manipulation.

SUBMITTER: Lin Y

PROVIDER: S-EPMC5908366 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs.

Lin Yao Y Wu Jiahua J Gu Weihuai W Huang Yulei Y Tong Zhongchun Z Huang Lijia L Tan Jiali J

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20180130 4

Targeted delivery of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system to the receptor cells is essential for in vivo gene editing. Exosomes are intensively studied as a promising targeted drug delivery carrier recently, while limited by their low efficiency in encapsulating of large nucleic acids. Here, a kind of hybrid exosomes with liposomes is developed via simple incubation. Different from the original exosomes, the resultant hybrid ...[more]

PMID: 29721412

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Project description:BackgroundGene therapy has held promises for treating specific genetic diseases. However, the key to clinical application depends on effective gene delivery.MethodsUsing a large animal model, we developed two pharmaceutical formulations for gene delivery in the pigs' vagina, which were made up of poly (β-amino ester) (PBAE)-plasmid polyplex nanoparticles (NPs) based two gel materials, modified montmorillonite (mMMT) and hectorite (HTT).FindingsBy conducting flow cytometry of the cervical cells, we found that PBAE-GFP-NPs-mMMT gel was more efficient than PBAE-GFP-NPs-HTT gel in delivering exogenous DNA intravaginally. Next, we designed specific CRISPR/SpCas9 sgRNAs targeting porcine endogenous retroviruses (PERVs) and evaluated the genome editing efficacy in vivo. We discovered that PERV copy number in vaginal epithelium could be significantly reduced by the local delivery of the PBAE-SpCas9/sgRNA NPs-mMMT gel. Comparable genome editing results were also obtained by high-fidelity version of SpCas9, SpCas9-HF1 and eSpCas9, in the mMMT gel. Further, we confirmed that the expression of topically delivered SpCas9 was limited to the vagina/cervix and did not diffuse to nearby organs, which was relatively safe with low toxicity.InterpretationOur data suggested that the PBAE-NPs mMMT vaginal gel is an effective preparation for local gene therapy, yielding insights into novel therapeutic approaches to sexually transmitted disease in the genital tract.FundingThis work was supported by the National Science and Technology Major Project of the Ministry of science and technology of China (No. 2018ZX10301402); the National Natural Science Foundation of China (81761148025, 81871473 and 81402158); Guangzhou Science and Technology Programme (No. 201704020093); National Ten Thousand Plan-Young Top Talents of China, Fundamental Research Funds for the Central Universities (17ykzd15 and 19ykyjs07); Three Big Constructions-Supercomputing Application Cultivation Projects sponsored by National Supercomputer Center In Guangzhou; the National Research FFoundation (NRF) South Africa under BRICS Multilateral Joint Call for Proposals; grant 17-54-80078 from the Russian Foundation for Basic Research.

Dataset Information

Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs.

Publications

Exosome-Liposome Hybrid Nanoparticles Deliver CRISPR/Cas9 System in MSCs.

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