Recent Advances in Mitochondria-Targeted Gene Delivery
Abstract
1. Introduction
2. Physical Approaches
3. Chemical Approaches
4. Biological Approaches
5. Combinatorial Approaches
6. Cargo DNAs
7. Applications as Disease Therapies
8. Concluding Remarks
Funding
Conflicts of Interest
References
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Classification | Key Acting Component | Delivery-Target Systems | Strategy | Advantages | Limitations | Ref. |
---|---|---|---|---|---|---|
Physical | Hydrodynamic injection | Rat, Mice | Cell penetration by hydrodynamic force | Simplicity | No mitochondria-targeting | [5,6,7] |
Biolistics | Yeast | Cell penetration by bombardment | Cell type-independent | Potential cell damage, No mitochondria-targeting | [8] | |
Chemical | Gemini surfactants | HeLa cell | Formation of cationic micelle-like structure with DNA | Works in small dose | Weak specificity to mitochondria | [9] |
Rhodamine 123 | Normal human dermal fibroblast (NHDF) adult donor cell | Precipitation of DNA using lipophilic molecule with delocalized positive charge | Can be traced due to fluorescence | Expression from transferred DNA has not been confirmed | [10,11] | |
DQAsomes | BT 20 cell | Transport of DNA by ampiphilic and cationic lipid-based vesicle | High specificity to mitochondria | Low transfection efficiency, Cytotoxicity | [12,13,14] | |
DQA80s | Primary human dermal fibroblasts, HeLa cell | Lipid incorporation into DQAsomes | Improved transfection efficiency | Delivery of DNA around mitochondria not into the matrix | [15] | |
MITO-Porter | HeLa cell, Rat | Membrane fusion by lipid-based nano carrier | Easy surface modification | [16,17,18,19] | ||
R8-MITO-Porter | Rat | Enhancing cellular uptake by functionalization with cationic peptide | High fusogenic activity with mitochondrial outer membrane | Low fusogenic activity with mitochondrial inner membrane, Moderate cytotoxicity | [16,17] | |
KALA-MITO-Porter | HeLa cell, Mice | Enhancing cellular uptake by functionalization with membrane destabilizing peptide | Improved transfection efficiency | High cytotoxicity | [19,20] | |
STPP-liposome | 4T1 cell, Mice | Conjugation of stearyl residue to lipophilic and cationic TPP for ampiphilic property | Selective accumulation in mitochondria | Cytotoxicity | [21] | |
TPP-PEG-PE liposome | HeLa, 4T1 cell, Mice | Substitution of stearyl moiety with biocompatible PEG-PE polymer | Decreased cytotoxicity | Transgene expression not confirmed | [22] | |
TPP-PAMAM dendrimer | HeLa, MCF-7, 4T1, NIH 3T3 cell | DNA condensation by high positive surface charge, endosomal escape by free tertiary amine groups | Efficient endosomal escape and high serum resistance | Transgene expression not confirmed | [23] | |
Biological | MTS-PNA | Myoblasts, Fibroblasts, NT 2, IMR 32, HeLa, HepG2, C2C12 cell | MTS-guided localization of DNA hybridized with PNA to mitochondria | High specificity to mitochondria via actions of translocase | Only can transfer short nucleic acids | [24,25] |
MTS-KH peptide | HEK 293 cell | Mitochondrial localization of MTS-conjugated DNA-binding peptide and exogenous DNA complex | Can transfer large DNA with high specificity to mitochondria | [26] | ||
MTS-AAV | Neuronal G11778A NT 2 cybrid, HEK 293T cell, Mice | Mitochondrial localization of DNA by inserting MTS into the AAV capsid | Proven effects of transgene expression | Inability to carry large DNA | [27,28] |
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Jang, Y.-h.; Lim, K.-i. Recent Advances in Mitochondria-Targeted Gene Delivery. Molecules 2018, 23, 2316. https://doi.org/10.3390/molecules23092316
Jang Y-h, Lim K-i. Recent Advances in Mitochondria-Targeted Gene Delivery. Molecules. 2018; 23(9):2316. https://doi.org/10.3390/molecules23092316
Chicago/Turabian StyleJang, Yoon-ha, and Kwang-il Lim. 2018. "Recent Advances in Mitochondria-Targeted Gene Delivery" Molecules 23, no. 9: 2316. https://doi.org/10.3390/molecules23092316
APA StyleJang, Y.-h., & Lim, K.-i. (2018). Recent Advances in Mitochondria-Targeted Gene Delivery. Molecules, 23(9), 2316. https://doi.org/10.3390/molecules23092316