Methods of reducing virus molecule levels
AssigneeAligos Therapeutics, Inc.
InventorsChia-Cheng Kao, Lawrence M. Blatt, Leonid Beigelman
Life of this patent
Estimating the term…
Abstract
Methods of reducing levels of virus molecules and/or treating viral infections include contacting cells with an oligonucleotide inhibitor that targets a cellular host factor that is a target RNA or target protein involved in viral replication. A pharmaceutical composition can include such an oligonucleotide inhibitor in an amount effective for treating an infection, such as a hepatitis B infection or a respiratory virus infection, such as a coronavirus infection.
Claims65
A method of reducing a level of a virus molecule produced by an infected cell, comprising:
- contacting the infected cell with an effective amount of an oligonucleotide inhibitor that targets a cellular host factor to thereby inhibit production of the cellular host factor by the infected cell and reduce the amount of the virus molecule produced by the infected cell;
- wherein the infected cell produces (a) at least one cellular host factor that is a target RNA or a target protein selected from a GRP78/BIP RNA, a GRP78/BIP protein, a SRSF1 RNA, a SRSF1 protein, a HNRNPA2B1 RNA, a HNRNPA2B1 protein, a RPLP1 RNA, a RPLP1 protein, a RPLP2 RNA, and a RPLP2 protein;
- and (b) an amount of at least one virus molecule that the virus utilizes for replication, wherein the virus molecule is a viral protein, a viral DNA or a viral RNA.
A method of treating a viral infection, comprising:
- administering a therapeutically effective amount of an oligonucleotide inhibitor to a subject in need thereof, wherein the oligonucleotide inhibitor targets a cellular host factor to thereby reduce production of the cellular host factor by infected cells of the subject;
- wherein the infected cells produce at least one cellular host factor that is a target RNA or a target protein selected from a GRP78/BIP RNA, a GRP78/BIP protein, a SRSF1 RNA, a SRSF1 protein, a HNRNPA2B1 RNA, a HNRNPA2B1 protein, a RPLP1 RNA, a RPLP1 protein, a RPLP2 RNA, and a RPLP2 protein.
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A pharmaceutical composition for treating a viral infection in a subject, comprising:
- a pharmaceutically acceptable carrier, diluent, excipient or combination thereof;
- and
- a therapeutically effective amount of an oligonucleotide inhibitor that targets a cellular host factor that is at least one of a target RNA or a target protein selected from a GRP78/BIP RNA, a GRP78/BIP protein, a SRSF1 RNA, a SRSF1 protein, a HNRNPA2B1 RNA, a HNRNPA2B1 protein, a RPLP1 RNA, a RPLP1 protein, a RPLP2 RNA, and a RPLP2 protein.
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An isolated synthetic oligonucleotide inhibitor comprising an antisense strand that hybridizes to a target RNA, wherein:
- the target RNA is selected from a GRP78/BIP RNA, a SRSF1 RNA, a HNRNPA2B1 RNA, a RPLP1 RNA, a RPLP2 RNA;
- and
- the antisense strand is any 15-21 mer antisense strand that can hybridize with high specificity to a 15-21 length section of the target RNA selected from:
- nucleobase 1379 to 1397 of the GRP78/BIP RNA,
- nucleobase 51 to 69 of the SRSF1 RNA,
- nucleobase 523 to 541 of the SRSF1 RNA,
- nucleobase 286 to 305 of the RPLP1 RNA,
- nucleobase 81 to 101 of the RPLP1 RNA,
- nucleobase 283 to 303 of the RPLP1 RNA,
- nucleobase 331 to 351 of the RPLP1 RNA,
- nucleobase −1 to 20 of the RPLP1 RNA,
- nucleobase 9 to 29 of the RPLP1 RNA,
- nucleobase 74 to 94 of the RPLP1 RNA,
- nucleobase 125 to 145 of the RPLP1 RNA,
- nucleobase 272 to 292 of the RPLP1 RNA,
- nucleobase 329 to 349 of the RPLP1 RNA,
- nucleobase 135 to 155 of the RPLP2 RNA,
- nucleobase 327 to 347 of the RPLP2 RNA,
- nucleobase 336 to 356 of the RPLP2 RNA,
- nucleobase 136 to 156 of the RPLP2 RNA,
- nucleobase 190 to 210 of the RPLP2 RNA,
- nucleobase 273 to 293 of the RPLP2 RNA,
- nucleobase 302 to 322 of the RPLP2 RNA,
- nucleobase 325 to 345 of the RPLP2 RNA,
- nucleobase 52 to 72 of the RPLP2 RNA,
- nucleobase 132 to 153 of the RPLP2 RNA,
- nucleobase 142 to 162 of the RPLP2 RNA,
- nucleobase 333 to 351 of the RPLP2 RNA,
- nucleobase 56 to 74 of the RPLP2 RNA,
- nucleobase 147 to 165 of the RPLP2 RNA,
- nucleobase 108 to 126 of the RPLP2 RNA, and
- nucleobase 120 to 138 of the RPLP2 RNA;
- wherein the nucleobases are numbered according to the positions numbered as shown for the respective target RNA as shown in FIG. 1A;
- and
- wherein the high specificity of hybridization is expressed by a calculated melting temperature (Tm) of 50° C. or higher.
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Dependencies are inferred from the claim text.