Efficient gene editing via non-viral delivery of CRISPR–Cas9 system using polymeric and hybrid microcarriers

Timin, Alexander S.; Muslimov, Аlbert R.; Lepik, Kirill V.; Epifanovskaya, Olga S.; Shakirova, Alena I.; Mock, Ulrike; Riecken, Kristoffer; Okilova, Maria V.; Sergeev, Vladislav S.; Afanasyev, Boris; Fehse, Boris; Sukhorukov, Gleb B.

doi:10.1016/j.nano.2017.09.001

Cited by 104 publications

(80 citation statements)

References 45 publications

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“…The basic principle of polymer carriers' synthesis is comprehensively described in the recent review article [22] and based on so-called layer-by-layer technique, which consists of deposition of oppositely charged polymers onto the sacrificial template [188]. After the dissolution of template, hollow polymer capsules can be produced, which in turn can be loaded with various bioactive compounds, such as drugs [189], nucleic acids [190], macromolecules [9], fluorescent moieties [191], and other. Generally, to impart polymer capsules properties of light sensitivity, their shell should be modified with plasmonic/dielectric NPs.…”

Section: Polymersmentioning

confidence: 99%

Optically responsive delivery platforms: from the design considerations to biomedical applications

et al. 2020

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Drug carriers with intelligent functions are powerful therapeutic and diagnostic platforms in curing various diseases such as malignant neoplasms. These functions include the remote noninvasive activation of drug using physical impacts, e.g. light exposure. Combination of different therapeutic modalities (chemotherapy, photodynamic therapy, and so forth) with light-responsive carriers enables promising synergetic effect in tumour treatment. The main goal of this review article is to provide the state of the art on light-sensitive delivery systems with the identification of future directions and their implementation in tumour treatment. In particular, this article reviews the general information on the physical and chemical fundamental mechanisms of interaction between light and carrier systems (e.g. plasmonic and dielectric nanoparticles), the design of optically responsive drug carriers (plain and composite), and the mechanisms of light-driven controlled release of bioactive compounds in biological environment. The special focus is dedicated to the most recent advances in optically responsive bioinspired drug vehicles.

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Section: Polymersmentioning

confidence: 99%

Optically responsive delivery platforms: from the design considerations to biomedical applications

et al. 2020

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“…Crosslinked PMA hydrogel and PMA/PLL capsules were used for successful encapsulation and release of siRNA in a reduced environment to target the cancer-related anti-apoptotic factor survinin [195]. DS/Parg microcapsules have also been reported as safe, efficient and non-viral delivery systems for the delivery of CRISPR-Cas9, a gene editing tool for the treatment of various genetic diseases [196]. The internalization of capsules labeled with cyanine-7 into HEK293T-d tomato cells was studied by CLSM and 3D reconstruction images.…”

Section: Delivery Of Nucleic Acidsmentioning

confidence: 99%

Multilayer capsules made of weak polyelectrolytes: a review on the preparation, functionalization and applications in drug delivery

Sharma¹,

Sundaramurthy²

2020

Beilstein J. Nanotechnol.

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Multilayer capsules have been of great interest for scientists and medical communities in multidisciplinary fields of research, such as drug delivery, sensing, biomedicine, theranostics and gene therapy. The most essential attributes of a drug delivery system are considered to be multi-functionality and stimuli responsiveness against a range of external and internal stimuli. Apart from the highly explored strong polyelectrolytes, weak polyelectrolytes offer great versatility with a highly controllable architecture, unique stimuli responsiveness and easy tuning of the properties for intracellular delivery of cargo. This review describes the progress in the preparation, functionalization and applications of capsules made of weak polyelectrolytes or their combination with biopolymers. The selection of a sacrificial template for capsule formation, the driving forces involved, the encapsulation of a variety of cargo and release based on different internal and external stimuli have also been addressed. We describe recent perspectives and obstacles of weak polyelectrolyte/biopolymer systems in applications such as therapeutics, biosensing, bioimaging, bioreactors, vaccination, tissue engineering and gene delivery. This review gives an emerging outlook on the advantages and unique responsiveness of weak polyelectrolyte based systems that can enable their widespread use in potential applications.

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“…22 Some studies have confirmed the efficiency of nonviral delivery to be equivalent to that of lentiviral systems, 23 and they represent promising safety and utility of gene editing. 24,25 Nonviral gene delivery could be highly efficient in ex vivo, including that asso-ciated with plasmid DNA and mRNA. 26 CRISPR/Cas9 delivery by the nonviral approach has some advantages and could partly avoid various concerns associated with viral-based delivery.…”

Section: Discussionmentioning

confidence: 99%

Gene Targeting of HPV18 E6 and E7 Synchronously by Nonviral Transfection of CRISPR/Cas9 System in Cervical Cancer

Ling

Yang

et al. 2020

Human Gene Therapy

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High-risk human papillomavirus (HPV) E6 and E7 genes display vital oncogenic properties in cervical cancer. Eliminating HPV driver gene or loss of function by the clustered regularly interspaced short palindromic repeat (CRISPR)/ Cas9 system is a promising treatment for the HPV-associated cancer. Thus, this study designed a CRISPR/Cas9 system to target the E6 and E7 genes at once, to detect whether it have efficacy in vitro and in vivo. Meanwhile, CRISPR/Cas9 system was measured after transfection with liposomes but virus. Cervical cancer lines (HeLa and SiHa) were used in this study. Sanger sequencing confirmed that the single CRISPR/Cas9 vector [termed E6E7-knockout (KO)] containing guide RNAs could targeting both HPV18 E6 and E7 genes in vitro. In addition, double-targeting E6 and E7 increased p53 protein expression significantly while compared with E6 or E7 targeting, respectively. Mice with xenografts were divided into four groups: three doses of experimental groups (20, 40, and 60 lg) and one control group. The E6E7-KO through liposome delivery was injected into tumors. Tumor growth was measured and protein expression was observed through immunohistochemistry. The toxic side effects in vivo were also evaluated. E6E7-KO induced cell apoptosis and inhibited cell proliferation markedly in vitro. E6E7-KO downregulated the messenger RNA and protein expression of E6 and E7, whereas p53 and p21 protein levels were upregulated accordingly. Notably, E6E7-KO delivery by liposome exhibited an effect in vivo. Tumor growth was inhibited in the E6E7-KO groups, which was accompanied by decreased E6/E7 protein expression and increased p53/p21 protein expression, especially the level of p53 protein expression. Therefore, E6E7-KO could have synergy efficient by p53 pathway. Furthermore, local injection with CRISPR/Cas9 by nonviral delivery may be regarded as a potential therapy for cervical cancer in the future.

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Efficient gene editing via non-viral delivery of CRISPR–Cas9 system using polymeric and hybrid microcarriers

Cited by 104 publications

References 45 publications

Optically responsive delivery platforms: from the design considerations to biomedical applications

Optically responsive delivery platforms: from the design considerations to biomedical applications

Multilayer capsules made of weak polyelectrolytes: a review on the preparation, functionalization and applications in drug delivery

Gene Targeting of HPV18 E6 and E7 Synchronously by Nonviral Transfection of CRISPR/Cas9 System in Cervical Cancer

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