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Title: Recoding method that removes inhibitory sequences and improves HIV gene expression

Patent ·
OSTI ID:1303730

The invention relates to inhibitory nucleotide signal sequences or "INS" sequences in the genomes of lentiviruses. In particular the invention relates to the AGG motif present in all viral genomes. The AGG motif may have an inhibitory effect on a virus, for example by reducing the levels of, or maintaining low steady-state levels of, viral RNAs in host cells, and inducing and/or maintaining in viral latency. In one aspect, the invention provides vaccines that contain, or are produced from, viral nucleic acids in which the AGG sequences have been mutated. In another aspect, the invention provides methods and compositions for affecting the function of the AGG motif, and methods for identifying other INS sequences in viral genomes.

Research Organization:
Institute for Advanced Study, Princeton, NJ (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
FG02-90ER40542
Assignee:
Institute of Advanced Study (Princeton, NJ)
Patent Number(s):
9,422,342
Application Number:
12/373,605
OSTI ID:
1303730
Resource Relation:
Patent File Date: 2007 Jul 12
Country of Publication:
United States
Language:
English

References (13)

Highly expressible genes patent May 2004
Adenovirus carrying gag gene HIV vaccine patent September 2004
Method of eliminating inhibitory/instability regions of mRNA patent September 2004
Packaging cells comprising codon-optimized gagpol sequences and lacking lentiviral accessory proteins patent October 2005
Viral vaccine composition, process, and methods of use patent-application May 2003
A Rev-Independent Human Immunodeficiency Virus Type 1 (HIV-1)-Based Vector That Exploits a Codon-Optimized HIV-1 gag-pol Gene journal May 2000
Coreceptor Tropism Can Be Influenced by Amino Acid Substitutions in the gp41 Transmembrane Subunit of Human Immunodeficiency Virus Type 1 Envelope Protein journal March 2008
Suppression of HIV replication by dominant negative mutants of HIV-1 (review). journal September 1998
Functional Surfaces of the Human Immunodeficiency Virus Type 1 Capsid Protein journal May 2003
A Recoding Method to Improve the Humoral Immune Response to an HIV DNA Vaccine journal September 2008
Increased Expression and Immunogenicity of Sequence-Modified Human Immunodeficiency Virus Type 1 gag Gene journal March 2000
Relative contributions of codon usage, promoter efficiency and leader sequence to the antigen expression and immunogenicity of HIV-1 Env DNA vaccine journal May 2006
Concerted Action of Multiple cis-Acting Sequences Is Required for Rev Dependence of Late Human Immunodeficiency Virus Type 1 Gene Expression journal November 2000

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