Disclosed herein are compositions that comprise engineered polynucleotides, pharmaceutical compositions comprising the same, methods of making the same, and methods of treatment comprising the compositions that comprise the engineered polynucleotides.

Recent advancements in LNA oligonucleotides include the use of amine linkers to link an LNA antisense oligonucleotide to a conjugate group. For example please see WO2014/I18267. The present invention originates from the identification of a problem when de-protecting LNA oligonucleotides which comprise an aliphatic amine group and DMF protected LNA G nucleoside, which results in the production of a +28 Da impurity. This problem is solved by using acyl protection groups on the exocyclic nitrogen of the LNA-G residue, rather than the standard DMF protection group.

CRISPR/Cas-related compositions and methods which provide for efficient gene editing of eukaryotic cells using modified gRNAs.

In the present invention, it has been confirmed that, when an RNA interference-inducing nucleic acid including at least one 8-oxoguanine (o.sup.8G) in 1st to 9th nucleotides from the 5′-end of at least one single strand of a double strand of a nucleic acid, and a modified nucleic acid that specifically binds to microRNA and in which at least one guanine (G) from among the 1st to 9th nucleotides from the 5′-end are modified with 8-oxoguanine (o.sup.8G), are produced and administered to cells or mice, various pathophysiological phenomena are induced.

In addition, the positions where G>T modifications occur have been identified in cDNA produced through the reverse transcription of microRNA in which guanine (G) is oxidatively modified with 8-oxoguanine (o.sup.8G) by oxidative stress in a seed region of microRNA, to confirm the positions where oxidative modification to 8-oxoguanine has occurred.

The present invention relates to a polynucleotide that comprises at least one phosphorothioate internucleoside linkage and at least one guanosine analogue comprising a guanine nucleobase analogue selected from the group consisting of: formula (I) and formula (II). Polynucleotides comprising such guanosine analogues show a relative reduced neurotoxicity compared to polynucleotides with natural guanosine.

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The present invention relates to RNA, particularly an immunostimulatory RNA (isRNA), a coding RNA or a combination thereof, for use in the treatment or prophylaxis of a disease, in particular a tumor and/or cancer disease. The present invention also provides pharmaceutical compositions, and a kit comprising the RNA(s). Further, the invention also comprises medical uses of the RNA(s) and compositions comprising the RNA(s).

Described herein are methods and compositions that provide highly efficient nucleic acid amplification. In some embodiments, this allows a 3-fold or greater increase of amplification product for each amplification cycle and therefore increased sensitivity and speed over conventional PCR. Modified bases can be employed in primers to provide this base-3 or greater amplification with satisfactory PCR cycle times, which are improved, as compared to those observed in the absence of modified bases.

The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.

The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

The present disclosure relates to immunogenic compositions comprising a varicella zoster vims (VZV) glycoprotein E antigen and a toll-like receptor 9 (TLR9) agonist, such as an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions are suitable for stimulating an immune response against VZV in an individual in need thereof.