The present invention relates to alkyne- and/or azide-modified mRNA, processes for producing such modified mRNA, cells which are transfected to include the modified mRNA, pharmaceutical compositions containing the modified mRNA or cells including the modified mRNA, and to uses of such mRNA, cells or pharmaceutical compositions in mRNA based therapeutic and/or prophylactic applications.

A modified oligonucleotide having an activity of inhibiting Ataxin 3 expression and having any one of the following nucleobase sequences or a nucleobase sequence of 17 contiguous bases contained in the nucleobase sequences:

TABLE-US-00001 (SEQ ID NO: 239) (1) TCGGGTAAGTAGATTTTC, (SEQ ID NO: 240) (2) GAAGTATCTGTAGGCCTA, (SEQ ID NO: 241) (3) GGACTGTATAGGAGATTA, (SEQ ID NO: 242) (4) GGTTATAGGATGCAGGTA, (SEQ ID NO: 243) (5) AGGTTATAGGATGCAGGT, (SEQ ID NO: 244) (6) GAAGCTAAGTAGGTGACT, (SEQ ID NO: 245) (7) TGAAGCTAAGTAGGTGAC, (SEQ ID NO: 246) (8) CCTAGTCACTTTGATAGA, (SEQ ID NO: 247) (9) GGAACATCTTGAGTAGGT, (SEQ ID NO: 248) (10) GGTGTTCAGGGTAGATGT, (SEQ ID NO: 249) (11) GGATACTCTGCCCTGTTC, (SEQ ID NO: 250) (12) GGTGTCAAACGTGTGGTT, (SEQ ID NO: 251) (13) CCGTGTGCTAGTATTTGT, (SEQ ID NO: 252) (14) TAGTAGAGTTTTGCTTGG, (SEQ ID NO: 253) (15) GATGTAGTAGAGTTTTGC, (SEQ ID NO: 254) (16) TGATGTAGTAGAGTTTTG, (SEQ ID NO: 255) (17) CTGATGTAGTAGAGTTTT, (SEQ ID NO: 256) (19) GCAAGTTGGTTTGTGGTA, (SEQ ID NO: 257) (20) TCTAGGCAATTGTGGTGG, (SEQ ID NO: 258) (21) GTAACTCTGCACTTCCCA, (SEQ ID NO: 259) (22) GTCATCCCTATGTCTTAT, (SEQ ID NO: 260) (23) GTCATATGGTCAGGGTAT, (SEQ ID NO: 261) (24) TGTCATATGGTCAGGGTA, (SEQ ID NO: 262) (25) ATGTCATATGGTCAGGGT, and (SEQ ID NO: 263) (26) TATGTCATATGGTCAGGG.

A modified oligonucleotide having an activity of inhibiting Ataxin 3 expression and having any one of the following nucleobase sequences or a nucleobase sequence of 17 contiguous bases contained in the nucleobase sequences:

TABLE-US-00001 (SEQ ID NO: 239) (1) TCGGGTAAGTAGATTTTC, (SEQ ID NO: 240) (2) GAAGTATCTGTAGGCCTA, (SEQ ID NO: 241) (3) GGACTGTATAGGAGATTA, (SEQ ID NO: 242) (4) GGTTATAGGATGCAGGTA, (SEQ ID NO: 243) (5) AGGTTATAGGATGCAGGT, (SEQ ID NO: 244) (6) GAAGCTAAGTAGGTGACT, (SEQ ID NO: 245) (7) TGAAGCTAAGTAGGTGAC, (SEQ ID NO: 246) (8) CCTAGTCACTTTGATAGA, (SEQ ID NO: 247) (9) GGAACATCTTGAGTAGGT, (SEQ ID NO: 248) (10) GGTGTTCAGGGTAGATGT, (SEQ ID NO: 249) (11) GGATACTCTGCCCTGTTC, (SEQ ID NO: 250) (12) GGTGTCAAACGTGTGGTT, (SEQ ID NO: 251) (13) CCGTGTGCTAGTATTTGT, (SEQ ID NO: 252) (14) TAGTAGAGTTTTGCTTGG, (SEQ ID NO: 253) (15) GATGTAGTAGAGTTTTGC, (SEQ ID NO: 254) (16) TGATGTAGTAGAGTTTTG, (SEQ ID NO: 255) (17) CTGATGTAGTAGAGTTTT, (SEQ ID NO: 256) (19) GCAAGTTGGTTTGTGGTA, (SEQ ID NO: 257) (20) TCTAGGCAATTGTGGTGG, (SEQ ID NO: 258) (21) GTAACTCTGCACTTCCCA, (SEQ ID NO: 259) (22) GTCATCCCTATGTCTTAT, (SEQ ID NO: 260) (23) GTCATATGGTCAGGGTAT, (SEQ ID NO: 261) (24) TGTCATATGGTCAGGGTA, (SEQ ID NO: 262) (25) ATGTCATATGGTCAGGGT, and (SEQ ID NO: 263) (26) TATGTCATATGGTCAGGG.

The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.

The present invention relates in part to nucleic acids, including nucleic acids encoding proteins, therapeutics and cosmetics comprising nucleic acids, methods for delivering nucleic acids to cells, tissues, organs, and patients, methods for inducing cells to express proteins using nucleic acids, methods, kits and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, therapeutics, and cosmetics produced using these methods, kits, and devices.

Disclosed herein are methods for decreasing AlAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, A1ATD associated liver disease, and pulmonary disease, such as, A1ATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting AlAT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, A1ATD associated liver disease and pulmonary disease, such as, A1ATD associated pulmonary disease.

Disclosed herein are methods for decreasing AlAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, A1ATD associated liver disease, and pulmonary disease, such as, A1ATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting AlAT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, A1ATD associated liver disease and pulmonary disease, such as, A1ATD associated pulmonary disease.

Methods and compositions for diagnosing and vaccinating against Ehrlichia canis and Ehrlichia chaffeensis are provided.

Methods and compositions for diagnosing and vaccinating against Ehrlichia canis and Ehrlichia chaffeensis are provided.

Provided is a double stranded RNA (dsRNA) compound comprising a guide strand and a passenger strand, the guide strand and the passenger strand each having a length of at least 300 basepairs (bp), the guide strand comprising a segment complementary to a target nucleic acid sequence of a target gene transcript. Also provided are methods of silencing a target gene transcript in a vertebrate cell or subject, of treating a pathogen infection in a subject, and of reducing replication or infectivity of a pathogen infection in the vertebrate cell or subject, respectively, comprising administering to the subject or cell a dsRNA compound, vector, conjugate or composition herein disclosed.