Materials and methods for prevention and treatment of RNA viral diseases
First Claim
1. A method of inhibiting an RNA virus infection in a patient, comprising administering to the patient:
- (a) a nucleotide sequence encoding at least one enzymatically active fragment of a 2′
-5′
oligoadenylate synthetase, wherein the nucleotide sequence is expressed in the patient;
or (b) at least one enzymatically active fragment of a 2′
-5′
oligoadenylate synthetase;
wherein the RNA virus is a type that transiently produces double-stranded RNA during intermediate replication; and
wherein the enzymatically active fragment of (a) and (b) comprises between 5 and 42 amino acids of SEQ ID NO;
2, SEQ ID NO;
4, SEQ ID NO;
6, SEQ ID NO;
8, SEQ ID NO;
10, or SEQ ID NO;
12;
or the enzymatically active fragment comprises at least 43 amino acids of SEQ ID NO;
2, SEQ ID NO;
4, SEQ ID NO;
6, SEQ ID NO;
8, SEQ ID NO;
10, or SEQ ID NO;
12.
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Accused Products
Abstract
The subject invention concerns a method of inhibiting an RNA virus infection within a patient by increasing the amount of 2-5 oligoadenylate synthetase (2-5 AS) activity within the patient. Preferably, the preventative and therapeutic methods of the present invention involve administering a nucleotide encoding 2-5 AS, or at least one catalytically active fragment thereof, such as the p40, p69, p100 subunits, to a patient in need thereof. The present inventors have determined that overexpression of 2-5AS causes a reduction in epithelial cell damage, reduction in infiltration of mononuclear cells in the peribronchiolar and perivascular regions, and reduction in thickening of the septa in the lungs. Levels of chemokines, such as MIP1-α, are also reduced upon overexpression of 2-5AS. The subject invention also pertains to pharmaceutical compositions containing a nucleotide sequence encoding 2-5 AS and a pharmaceutically acceptable carrier, as well as vectors for delivery of the 2-5 AS nucleotide sequence.
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Citations
24 Claims
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1. A method of inhibiting an RNA virus infection in a patient, comprising administering to the patient:
- (a) a nucleotide sequence encoding at least one enzymatically active fragment of a 2′
-5′
oligoadenylate synthetase, wherein the nucleotide sequence is expressed in the patient;
or (b) at least one enzymatically active fragment of a 2′
-5′
oligoadenylate synthetase;
wherein the RNA virus is a type that transiently produces double-stranded RNA during intermediate replication; and
wherein the enzymatically active fragment of (a) and (b) comprises between 5 and 42 amino acids of SEQ ID NO;
2, SEQ ID NO;
4, SEQ ID NO;
6, SEQ ID NO;
8, SEQ ID NO;
10, or SEQ ID NO;
12;
or the enzymatically active fragment comprises at least 43 amino acids of SEQ ID NO;
2, SEQ ID NO;
4, SEQ ID NO;
6, SEQ ID NO;
8, SEQ ID NO;
10, or SEQ ID NO;
12. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24)
- (a) a nucleotide sequence encoding at least one enzymatically active fragment of a 2′
Specification
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- Resources
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Current AssigneeUniversity of South Florida (State University System of Florida)
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Original AssigneeUniversity of South Florida (State University System of Florida)
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InventorsMohapatra, Shyam S., Behera, Aruna K.
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Primary Examiner(s)ZARA, JANE J
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Application NumberUS12/638,800Publication NumberTime in Patent Office1,043 DaysField of Search435/6, 435/91.1, 435/91.31, 435/455, 435/375, 514/1, 514/2, 514/44, 536/23.1, 536/24.5, 536/23.2, 530/300, 530/350US Class Current514/44CPC Class CodesA61K 38/217 IFN-gammaA61K 38/45 Transferases (2)A61K 38/51 Lyases (4)A61K 48/00 Medicinal preparations cont...A61K 48/005 characterised by an aspect ...A61P 31/14 for RNA virusesC12N 2710/10343 viral genome or elements th...C12N 2799/022 where the vector is derived...C12N 9/1241 Nucleotidyltransferases (2....
