Inhibiting HIV by HIV-1 Protease-activated Maize Ribosome-inactivating Protein and the Procedure of Generating the Protein
For a drug to eliminate HIV-infected cells, a major challenge is to achieve high specificity toward target cells but low cytotoxicity toward normal cells. Maize ribosome-inactivating protein (RIP) contains a 25-amino acid internal inactivation region. Removal of this region generates the active cytotoxin. We have taken advantage of this maturation mechanism and increase the specificity of maize RIP toward HIV-infected cells by substituting the internal inactivation region with a combination of HIV-1 protease cleavage sites. Two variants generated were found to be activated by recombinant HIV-1 protease in vitro and in HIV-infected cells. They also inhibited the replication of HIV-1. On the other hand, these variants had low cytotoxicity towards uninfected C8166 cells. Our work of adding the HIV-1 cleavage sites to the internal inactivation region of maize RIP may serve as a platform for inhibiting other pathogens that require a specific protease for their function.
Inventor: WANG, Rui-rui | HUANG, Jin-bo | SHAO, Peng-zhu | LUO, Jia-yi | ZHENG, Yong-tang | MAI, Ya-si
Priority Number: CN102234638B
IPC Current: C12N000924 | A61K003847 | A61K004800 | A61P003112 | C12N001556 | C12N001563
Assignee Applicant: Kunming Institute of Zoology Chinese Academy of Sciences | The Chinese The University of Hong Kong
Title: Modified maize ribosome-inactivating protein precursor and application as well as protein purification method thereof
Usefulness: Modified maize ribosome-inactivating protein precursor and application as well as protein purification method thereof
Summary: The modified maize ribosome inactivating protein precursor and vector are used for preparing a medical composition for treating viral infection selected from rhinovirus infection, adenovirus infection, coronavirus infection, HIV infection, simian immunodeficiency virus (SIV) infection, herpes virus infection, human T lymphocyte virus infection, West Nile viral infection, hepatitis C virus infection, preferably HIV-1 infection and HIV-2 infection, in a subject (all claimed).
Novelty: New modified maize ribosome inactivating protein precursor comprises a modified internal inactive region comprising restriction enzyme cutting site, useful for treating viral infection, e.g. HIV-1 and HIV-2 infection
生物醫學
DNA /基因工程
09/SCI/331
Inventor(s): Professor P C SHAW, Department of Biochemistry
Patent Status: Chinese Patent Application Pending Licensing Status: Available for licensing
香港
