monkey liver
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2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Liping Zhong ◽  
Yong Huang ◽  
Jian He ◽  
Nuo Yang ◽  
Banghao Xu ◽  
...  

AbstractNon-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.


2021 ◽  
Vol 161 ◽  
pp. 105807
Author(s):  
Shiori Honda ◽  
Tatsuki Fukami ◽  
Takuya Tsujiguchi ◽  
Yongjie Zhang ◽  
Masataka Nakano ◽  
...  

Bioanalysis ◽  
2019 ◽  
Vol 11 (21) ◽  
pp. 1955-1965 ◽  
Author(s):  
Jing Li ◽  
Ju Liu ◽  
Jennifer Enders ◽  
Michael Arciprete ◽  
Chris Tran ◽  
...  

Aim: A novel single-stranded deaminated oligonucleotide metabolite resulting from a REVERSIR™ oligonucleotide was discovered and identified in monkey liver after subcutaneous administration. Results & methodology: REVERSIR-A and its metabolites were extracted from biological matrices by solid phase extraction and analyzed using LC coupled with high-resolution MS under negative ionization mode. A novel 9-mer metabolite of REVERSIR-A, resulting from deamination of the 3′ terminal 2′- O-methyl-adenosine nucleotide to 2′- O-methyl-inosine, was discovered at significant levels in monkey liver. The metabolite's identity was confirmed by LC–MS/MS. Conclusion: This report describes the first observation of a long-chain deaminated metabolite of a single-stranded REVERSIR oligonucleotide in vivo in monkey liver.


Xenobiotica ◽  
2013 ◽  
Vol 43 (12) ◽  
pp. 1037-1042 ◽  
Author(s):  
Masahiro Utoh ◽  
Norie Murayama ◽  
Yasuhiro Uno ◽  
Yui Onose ◽  
Shinya Hosaka ◽  
...  

2012 ◽  
Vol 84 (12) ◽  
pp. 1691-1695 ◽  
Author(s):  
Yoshio Hosoi ◽  
Yasuhiro Uno ◽  
Norie Murayama ◽  
Hideki Fujino ◽  
Mitsunori Shukuya ◽  
...  

Xenobiotica ◽  
2010 ◽  
Vol 40 (9) ◽  
pp. 621-629 ◽  
Author(s):  
Shotaro Uehara ◽  
Norie Murayama ◽  
Hiroshi Yamazaki ◽  
Yasuhiro Uno

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