A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting

Yamada, Yuma; Furukawa, Ryo; Harashima, Hideyoshi

doi:10.1016/j.xphs.2016.03.002

Cited by 38 publications

(27 citation statements)

References 35 publications

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“…These findings suggest that mitochondrial specific delivery via the RP aptamer of the RP/KALA-MITO-Porter is necessary for G625A fibroblasts, which have low mitochondrial membrane potentials, rather than by mitochondrial delivery by the KALA-MITO-Porter via electrostatic interactions. We previously found a similar phenomenon wherein a RP-modified R8-MITO-Porter accumulated in mitochondria more efficiently than a RP-unmodified one [10]. Collectively, we conclude that RP aptamer modification enhanced both the cellular uptake and mitochondrial targeting of the KALA-MITO-Porter in G625A fibroblasts, contributing to the enhancement of mitochondrial transfection in G625A fibroblasts.…”

Section: Discussionsupporting

confidence: 72%

“…The use of an excess amount of RNA aptamer (6.0 mol%) might mask, even the head group of the KALA displayed on the RP aptamer coated carrier-surface, resulting in a decrease in cellular uptake. Such an optimal value was also observed when the RP/R8-MITO-Porter was used in the case of HeLa cells [10]. We speculate that the cellular uptake decreased at a 2.5% RP aptamer modification, because the charge was neutralized ( Figure S5), so that the stability of the carriers decreased and aggregation easily occurred in the culture medium.…”

Section: Discussionsupporting

confidence: 53%

“…Given this situation, we attempted to use an RP aptamer, which is a negatively charged mitochondrial RNA aptamer that can enhance mitochondrial targeting, as a mitochondrial targeting ligand of the KALA-MITO-Porter. Our previous studies showed that modification of the R8-MITO-Porter with the RP aptamer enhanced cellular uptake and mitochondrial targeting in HeLa cells [10]. As shown in Figure 5, modification of the KALA-MITO-Porter with 4 mol% of the aptamer caused a significant increase in the cellular uptake values compared with the RPunmodified KALA-MITO-Porter.…”

Section: Discussionmentioning

confidence: 81%

“…aptamer, a mitochondrial RNA aptamer that enhances cellular uptake and mitochondrial targeting [10].…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease

Ishikawa

Somiya

Munechika

et al. 2018

Journal of Controlled Release

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To achieve mitochondrial gene therapy, developing a mitochondrial transgene expression system that produces therapeutic proteins in mitochondria of disease cells is essential. We previously reported on the design of pCMV-mtLuc (CGG) containing a CMV promotor and a NanoLuc (Nluc) luciferase gene that records adjustments to the mitochondrial codon system, and showed that the mitochondrial transfection of pCMV-mtLuc (CGG) resulted in the efficient production of the Nluc luciferase protein in human HeLa cells. This mitochondrial transfection was achieved using a MITO-Porter, a liposome-based carrier for delivering a cargo to mitochondria via membrane fusion. We report herein that mitochondrial transfection using the MITO-Porter results in mitochondrial transgene expression in G625A fibroblasts obtained from a patient with a mitochondrial disease. We investigated the effect of promoters and the basic structure of pCMV-mtLuc (CGG) on gene expression efficiency, and were able to construct a high performance mitochondrial DNA vector, pCMV-mtLuc (CGG) [hND4] that contains a human mitochondrial endogenous gene. We also constructed an RP/KALA-MITO-Porter composed of the KALA peptide (cell-penetrating peptide) with a mitochondrial RNA aptamer to enhance cellular uptake and mitochondrial targeting. Finally, the mitochondrial transfection of pCMV-mtLuc (CGG) [hND4] in G625A fibroblasts using the RP/KALA-MITO-Porter resulted in strong mitochondrial transgene expression.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 81%

“…aptamer, a mitochondrial RNA aptamer that enhances cellular uptake and mitochondrial targeting [10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease

Ishikawa

Somiya

Munechika

et al. 2018

Journal of Controlled Release

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“…To date, various types of lipid carriers have been described that are characterized by different lipid composition and parameters of transfection efficacy. The next step in improving the nanocarrier design will be the use of specific mitochondria‐targeting molecules 89,109,110 …”

Section: Lipid Carriers For Gene Delivery To Mitochondriamentioning

confidence: 99%

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

Zakirov

Zhang

Grechko

et al. 2020

Pharmacology Res & Perspec

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Atherosclerosis with associated cardiovascular diseases remains one of the main causes of disability and death worldwide, requiring development of new solutions for prevention and treatment. Macrophages are the key effectors of a series of events involved in atherogenesis, such as inflammation, plaque formation, and changes in lipid metabolism. Some of these events were shown to be associated with mitochondrial dysfunction and excessive mitochondrial DNA (mtDNA) damage. Moreover, macrophages represent a promising target for novel therapeutic approaches that are based on the expression of various receptors and nanoparticle uptake. Lipid‐based gene delivery to mitochondria is considered to be an interesting strategy for mtDNA damage correction. To date, several nanocarriers and their modifications have been developed that demonstrate high transfection efficiency and low cytotoxicity. This review discusses the possibilities of lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy.

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Cell-Penetrating Peptides

Zorko

Langel

2021

Methods in Molecular Biology

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A Dual-Ligand Liposomal System Composed of a Cell-Penetrating Peptide and a Mitochondrial RNA Aptamer Synergistically Facilitates Cellular Uptake and Mitochondrial Targeting

Cited by 38 publications

References 35 publications

Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease

Mitochondrial transgene expression via an artificial mitochondrial DNA vector in cells from a patient with a mitochondrial disease

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

Cell-Penetrating Peptides

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