scholarly journals Efficient Messenger RNA Delivery to the Kidney Using Renal Pelvis Injection in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1810
Author(s):  
Natsuko Oyama ◽  
Maho Kawaguchi ◽  
Keiji Itaka ◽  
Shigeru Kawakami
Keyword(s):  
Renal Pelvis ◽  
Plasmid Dna ◽  
Messenger Rna ◽  
Viral Vectors ◽  
Protein Production ◽  
Target Cells ◽  
Gene Therapies ◽  
Naked Plasmid ◽  
Mrna Therapeutics ◽  
Naked Plasmid Dna

Renal dysfunction is often associated with the inflammatory cascade, leading to non-reversible nephrofibrosis. Gene therapy has the ability to treat the pathology. However, the difficulty in introducing genes into the kidney, via either viral vectors or plasmid DNA (pDNA), has hampered its extensive clinical use. Messenger RNA (mRNA) therapeutics has recently attracted attention as alternative gene therapies. mRNA allows protein production into post-mitotic cells without the need for transport to the nuclei in the target cells. However, few studies have reported the delivery of mRNA to the kidney. In this study, we attempted to deliver mRNA to the kidney based on the principle of pressure stimulation, by administering mRNA-loaded polyplex nanomicelles via a renal pelvis injection, directly into the kidney. Compared with the administration of naked plasmid DNA (pDNA) and naked mRNA, the mRNA-loaded nanomicelles diffusely induced protein expression in a greater number of cells at the tubular epithelium for some days. The plasma creatinine (Cre) and blood urea nitrogen (BUN) levels after the administration remained similar to those of the sham-operated controls, without marked changes in histological sections. The safety and efficacy of mRNA-loaded nanomicelles would make distinct contributions to the development of mRNA therapeutics for the kidney.

In vivo expression and antitumor activity of p53 gene transfer with naked plasmid DNA in an ovarian cancer xenograft model in nude mice

2006 ◽  
Vol 32 (5) ◽  
pp. 449-453 ◽  
Author(s):  
Pierre Collinet ◽  
Rodolphe Vereecque ◽  
Frédéric Sabban ◽  
Denis Vinatier ◽  
Eric Leblanc ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Transfer ◽  
Antitumor Activity ◽  
Nude Mice ◽  
Plasmid Dna ◽  
Xenograft Model ◽  
P53 Gene ◽  
Naked Plasmid ◽  
Naked Plasmid Dna

scholarly journals Rubbing Gastric Serosal Surface Enhances Naked Plasmid DNA Transfer in Rats and Mice

2011 ◽  
Vol 34 (9) ◽  
pp. 1514-1517 ◽  
Author(s):  
Toyoharu Mine ◽  
Hiroki Ishii ◽  
Sayuri Nakajima ◽  
Naoki Yoshikawa ◽  
Hirotaka Miyamoto ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Dna Transfer ◽  
Serosal Surface ◽  
Naked Plasmid ◽  
Rats And Mice ◽  
Naked Plasmid Dna

scholarly journals Sequence Determinants in Gammaretroviral Env Cytoplasmic Tails Dictate Virus-Specific Pseudotyping Compatibility

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Yul Eum Song ◽  
Grace Y. Olinger ◽  
Sanath Kumar Janaka ◽  
Marc C. Johnson
Keyword(s):  
Viral Vectors ◽  
Leukemia Virus ◽  
Target Cells ◽  
Gag Protein ◽  
Factors Affecting ◽  
Gene Therapies ◽  
Viral Glycoproteins ◽  
Cytoplasmic Tails ◽  
Specific Manner ◽  
Hiv 1

ABSTRACTViruses can incorporate foreign glycoproteins to form infectious particles through a process known as pseudotyping. However, not all glycoproteins are compatible with all viruses. Despite the fact that viral pseudotyping is widely used, what makes a virus/glycoprotein pair compatible is poorly understood. To study this, we chose to analyze a gammaretroviral glycoprotein (Env) whose compatibility with different viruses could be modulated through small changes in its cytoplasmic tail (CT). One form of this glycoprotein is compatible with murine leukemia virus (MLV) particles but incompatible with human immunodeficiency virus type 1 (HIV-1) particles, while the second is compatible with HIV-1 particles but not with MLV particles. To decipher the factors affecting virus-specific Env incompatibility, we characterized Env incorporation, maturation, cell-to-cell fusogenicity, and virus-to-cell fusogenicity of each Env. The HIV-1 particle incompatibility correlated with less efficient cleavage of the R peptide by HIV-1 protease. However, the MLV particle incompatibility was more nuanced. MLV incompatibility appeared to be caused by lack of incorporation into particles, yet incorporation could be restored by further truncating the CT or by using a chimeric MLV Gag protein containing the HIV-1 MA without fully restoring infectivity. The MLV particle incompatibility appeared to be caused in part by fusogenic repression in MLV particles through an unknown mechanism. This study demonstrates that the Env CT can dictate functionality of Env within particles in a virus-specific manner.IMPORTANCEViruses utilize viral glycoproteins to efficiently enter target cells during infection. How viruses acquire viral glycoproteins has been studied to understand the pathogenesis of viruses and develop safer and more efficient viral vectors for gene therapies. The CTs of viral glycoproteins have been shown to regulate various stages of glycoprotein biogenesis, but a gap still remains in understanding the molecular mechanism of glycoprotein acquisition and functionality regarding the CT. Here, we studied the mechanism of how specific mutations in the CT of a gammaretroviral envelope glycoprotein distinctly affect infectivity of two different viruses. Different mutations caused failure of glycoproteins to function in a virus-specific manner due to distinct fusion defects, suggesting that there are virus-specific characteristics affecting glycoprotein functionality.

scholarly journals Naked plasmid DNA transfer to the porcine liver using rapid injection with large volume

Gene Therapy ◽  
2006 ◽  
Vol 13 (24) ◽  
pp. 1696-1702 ◽  
Author(s):  
H Yoshino ◽  
K Hashizume ◽  
E Kobayashi
Keyword(s):  
Large Volume ◽  
Plasmid Dna ◽  
Dna Transfer ◽  
Porcine Liver ◽  
Rapid Injection ◽  
Naked Plasmid ◽  
Naked Plasmid Dna

scholarly journals Pretreatment with Epidermal Growth Factor Enhances Naked Plasmid DNA Transfer onto Gastric Serosal Surface in Mice

2012 ◽  
Vol 35 (6) ◽  
pp. 903-908 ◽  
Author(s):  
Hirotaka Miyamoto ◽  
Sumie Baba ◽  
Sayuri Nakajima ◽  
Toyoharu Mine ◽  
Naoki Yoshikawa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Plasmid Dna ◽  
Dna Transfer ◽  
Serosal Surface ◽  
Epidermal Growth ◽  
Naked Plasmid ◽  
Naked Plasmid Dna

Percutaneous Pulmonary Artery Gene Transfer in Pigs Using Naked Plasmid DNA Delivered During Angioplasty

2000 ◽  
Vol 21 (3) ◽  
pp. 223-227 ◽  
Author(s):  
L.H. Keller ◽  
R. Vander Heide ◽  
K.A. Pebbles ◽  
T.J. L'Ecuyer
Keyword(s):  
Gene Transfer ◽  
Pulmonary Artery ◽  
Plasmid Dna ◽  
Naked Plasmid ◽  
Naked Plasmid Dna
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