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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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