Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases

Huang, Mei; Sun, Rui; Huang, Qiang; Tian, Zhigang

doi:10.3389/fphar.2017.00591

Cited by 25 publications

(16 citation statements)

References 131 publications

(125 reference statements)

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“…HGD is widely accepted as an efficient method that enables the in vivo transfer of NAs into mouse hepatocytes via the caudal vein [42,43]. Gene delivery to the kidneys and lungs is also possible with this method, although the transfection efficiency is low and the number of transferred NAs appears to be low, in the case of a successful transfection [9].…”

Section: Discussionmentioning

confidence: 99%

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Nakamura

Ando

2020

Nanomaterials

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We previously reported that heparin/protamine particles (LHPPs) produced as nanoparticles through simple mixing of raw materials exhibit sustained protein release and can be retained in cells. In the present study, we modified LHPPs without employing any organic synthetic approach. The resulting LHPPs were re-named as improved LHPPs (i-LHPPs) and have the ability to retain cell-penetrating peptides (GRKKRRQRRRPPQ) based on electrostatic interactions. We examined whether i-LHPPs can introduce exogenous proteins (i.e., lacZ protein encoding bacterial β-galactosidase) into cultured cells in vitro, or into murine hepatocytes in vivo through intravenous injection to anesthetized mice. We found an accumulation of the transferred protein in both in vitro cultured cells and in vivo hepatocytes. To the best of our knowledge, reports of successful in vivo delivery to hepatocytes are rare. The i-LHPP-based protein delivery technique will be useful for in vivo functional genetic modification of mouse hepatocytes using Cas9 protein-mediated genome editing targeting specific genes, leading to the creation of hepatic disease animal models for research that aims to treat liver diseases.

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Section: Discussionmentioning

confidence: 99%

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Nakamura

Ando

2020

Nanomaterials

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“…To obtain this, we employed the PB system, which allows chromosomal integration of an exogenous DNA of approximately 10 kb in size [ 20 ]. It has been reported that the expression of a chromosomally integrated GOI via the PB system continued over 300 days [ 33 ], and that HGD-mediated gene delivery of a naked plasmid in the liver confers the GOI an expression lasting for approximately 4 weeks [ 2 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Intravenous Delivery of piggyBac Transposons as a Useful Tool for Liver-Specific Gene-Switching

Nakamura

Watanabe

Ando

et al. 2018

IJMS

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Hydrodynamics-based gene delivery (HGD) is an efficient method for transfecting plasmid DNA into hepatocytes in vivo. However, the resulting gene expression is transient, and occurs in a non-tissue specific manner. The piggyBac (PB) transposon system allows chromosomal integration of a transgene in vitro. This study aimed to achieve long-term in vivo expression of a transgene by performing hepatocyte-specific chromosomal integration of the transgene using PB and HGD. Using this approach, we generated a novel mouse model for a hepatic disorder. A distinct signal from the reporter plasmid DNA was discernible in the murine liver approximately two months after the administration of PB transposons carrying a reporter gene. Then, to induce the hepatic disorder, we first administered mice with a PB transposon carrying a CETD unit (loxP-flanked stop cassette, diphtheria toxin-A chain gene, and poly(A) sites), and then with a plasmid expressing the Cre recombinase under the control of a liver-specific promoter. We showed that this system can be used for in situ manipulation and analysis of hepatocyte function in vivo in non-transgenic (Tg) animals.

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“…However, the results remain inferior compared with those achieved using genome integration via viral vectors. This problem, the gene transfer efficiency of nonviral vectors, has been further addressed by the development of devices that allow for continuous injection of DNA deep into the body, such as into the liver [ 49 , 50 ]. Although these devices are clearly useful, typically, the treatment of genetic deficiencies must continue throughout life, such that nonviral delivery might never be as convenient or effective as viral-mediated integration of DNA into the genome.…”

Section: Efficiency Of Gene Therapy With Nonviral Vectorsmentioning

confidence: 99%

Nonviral Gene Therapy for Cancer: A Review

Hidai

Kitano

2018

Diseases

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Although the development of effective viral vectors put gene therapy on the road to commercialization, nonviral vectors show promise for practical use because of their relative safety and lower cost. A significant barrier to the use of nonviral vectors, however, is that they have not yet proven effective. This apparent lack of interest can be attributed to the problem of the low gene transfer efficiency associated with nonviral vectors. The efficiency of gene transfer via nonviral vectors has been reported to be 1/10th to 1/1000th that of viral vectors. Despite the fact that new gene transfer methods and nonviral vectors have been developed, no significant improvements in gene transfer efficiency have been achieved. Nevertheless, some notable progress has been made. In this review, we discuss studies that report good results using nonviral vectors in vivo in animal models, with a particular focus on studies aimed at in vivo gene therapy to treat cancer, as this disease has attracted the interest of researchers developing nonviral vectors. We describe the conditions in which nonviral vectors work more efficiently for gene therapy and discuss how the goals might differ for nonviral versus viral vector development and use.

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Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases

Cited by 25 publications

References 131 publications

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Development of Novel Heparin/Protamine Nanoparticles Useful for Delivery of Exogenous Proteins In Vitro and In Vivo

Intravenous Delivery of piggyBac Transposons as a Useful Tool for Liver-Specific Gene-Switching

Nonviral Gene Therapy for Cancer: A Review

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