The disclosure includes antisense oligonucleotides, including gapmer antisense oligonucleotides, along with methods of making and use, e.g., against HBV.

Provided are peptide nucleic acid derivatives targeting a 3′ splice site of the human tyrosinase pre-mRNA. The peptide nucleic acid derivatives potently induce a splice variant of the human tyrosinase mRNA in cells, and are useful to safely treat dermatological indications or conditions involving the human tyrosinase protein upon topical administration.

Provided are peptide nucleic acid derivatives targeting a 3′ splice site of the human tyrosinase pre-mRNA. The peptide nucleic acid derivatives potently induce a splice variant of the human tyrosinase mRNA in cells, and are useful to safely treat dermatological indications or conditions involving the human tyrosinase protein upon topical administration.

The invention provides compositions and methods of making and using effector oligonucleotides, including effector oligonucleotides with greater than one mismatch as compared to its target sequence. These effector oligonucleotides are useful for improving the efficiency of genomic editing as well as providing therapeutic benefits to individuals in need thereof.

The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.

Disclosed an improved process for synthesising a nucleic acid strand using cycles of template independent enzyme extension. Having one or more of the amino groups on the base heterocyclic groups masked with protecting groups helps to prevent secondary structure in the extended strand, thereby improving access of the enzyme to the 3′ OH terminus for extension.

The present disclosure relates to methods of treating heat stock factor 1 (HSF1)-related diseases such as cancer, autoimmune and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

The current invention provides an improved oligonucleotide and its use for treating, ameliorating, preventing, delaying and/or treating a human cis-element repeat instability associated genetic neuromuscular or neurodegenerative disorder.

The invention provides immunomodulatory polynucleotides and methods for immunomodulation of individuals using the immunomodulatory polynucleotides.

Provided herein are compositions, systems, articles of manufacture, and methods of treating a subject with: i) an APE2 inhibitor, and ii) a drug agent that causes increased expression of APE2 in said subject. In certain embodiments, the drug agent is Cisplatin or similar drug.