Plasmid DNA and Messenger RNA for Therapy

Author(s):  
Steve Pascolo
Keyword(s):  
2018 ◽  
Vol 10 (38) ◽  
pp. 31915-31927 ◽  
Author(s):  
Yuyuan Wang ◽  
Ben Ma ◽  
Amr A. Abdeen ◽  
Guojun Chen ◽  
Ruosen Xie ◽  
...  

Nanomaterials ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 364 ◽  
Author(s):  
Itziar Gómez-Aguado ◽  
Julen Rodríguez-Castejón ◽  
Mónica Vicente-Pascual ◽  
Alicia Rodríguez-Gascón ◽  
María Ángeles Solinís ◽  
...  

The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.


2020 ◽  
Vol 4 (5) ◽  
pp. 2000057 ◽  
Author(s):  
Heyang Zhang ◽  
Koen Rombouts ◽  
Laurens Raes ◽  
Ranhua Xiong ◽  
Stefaan C. De Smedt ◽  
...  

2008 ◽  
Vol 115 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Benjamin Weide ◽  
Claus Garbe ◽  
Hans-Georg Rammensee ◽  
Steve Pascolo

2020 ◽  
Vol 8 (11) ◽  
pp. 3063-3071
Author(s):  
Jungju Oh ◽  
Sang-Mi Kim ◽  
Eun-Hye Lee ◽  
Minkyung Kim ◽  
Youngki Lee ◽  
...  

Heme oxygenase-1 messenger RNA (HO1-mRNA) was delivered into the post-ischemic brain, using a polymeric carrier. Therapeutic efficacy of HO1-mRNA delivery was compared with that of HO1-plasmid DNA (HO1-pDNA) in ischemia-reperfusion rat models.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1810
Author(s):  
Natsuko Oyama ◽  
Maho Kawaguchi ◽  
Keiji Itaka ◽  
Shigeru Kawakami

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.


Author(s):  
G. W. Hacker ◽  
I. Zehbe ◽  
J. Hainfeld ◽  
A.-H. Graf ◽  
C. Hauser-Kronberger ◽  
...  

In situ hybridization (ISH) with biotin-labeled probes is increasingly used in histology, histopathology and molecular biology, to detect genetic nucleic acid sequences of interest, such as viruses, genetic alterations and peptide-/protein-encoding messenger RNA (mRNA). In situ polymerase chain reaction (PCR) (PCR in situ hybridization = PISH) and the new in situ self-sustained sequence replication-based amplification (3SR) method even allow the detection of single copies of DNA or RNA in cytological and histological material. However, there is a number of considerable problems with the in situ PCR methods available today: False positives due to mis-priming of DNA breakdown products contained in several types of cells causing non-specific incorporation of label in direct methods, and re-diffusion artefacts of amplicons into previously negative cells have been observed. To avoid these problems, super-sensitive ISH procedures can be used, and it is well known that the sensitivity and outcome of these methods partially depend on the detection system used.


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