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Catalytically Hyperactive Variant of Human APOBEC3G Protein

Summary
The National Cancer Institute (NCI) seeks co-development and licensing interest to further develop and optimize APOBEC3G protein variants.
NIH Reference Number
E-150-2018
Product Type
Keywords
  • APOBEC3G, ssDNA, AIDS, Gene Editing, CTD2, Genetically disordered diseases, Matsuo
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

Researchers at the National Cancer Institute (NCI) have developed a highly active variant of the catalytic domain APOBEC3G with higher ssDNA affinity. This variant may be used to develop therapeutics for AIDS, and may also be used as a tool of gene editing techniques. This hyperactive variant of the human APOBEC3G protein (hereby called CTD2) can be used as a tool to edit human genes in combination with the CRISPR/Cas9 system. CTD2 is selective to a specific target DNA sequence, soluble, and catalytically hyperactive, which makes CTD2 the ideal molecule to use in the aforementioned gene editing, using the CRISPR/Cas9 system. 

Figure: Antiviral restriction activity of FLAG-NTD-CTD2

Antiviral restriction activity of FLAG-NTD-CTD2

Potential Commercial Applications
  • Therapeutic for HIV
  • Gene Editing
Competitive Advantages
  • The variant of the catalytic domain of APOBEC3G has high affinity to ssDNA substrates as apparent dissociation constant, Kd, is 55 µM
  • The variant of the catalytic domain of APOBEC3G can catalyze deamination of cytosines in single stranded DNA 20 times faster than the wild type catalytic domain of APOBEC3G
  • The variant of the catalytic domain of APOBEC3G is 4 times more soluble than the wild type catalytic domain of APOBEC3G
Publications

Maiti A, et al. Crystal structure of the catalytic domain of HIV-1 restriction factor APOBEC3G in complex with ssDNA.  [PMID 29941968]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/673,591 , Filed 18 May 2018
Therapeutic Area
Updated
Monday, October 15, 2018