Nucleic acid molecules and uses thereof

A method of stimulating an anti-Norovirus immune response in a mammalian subject comprising administering to the subject a pharmaceutical composition comprising at least three artificial RNA molecules comprising:

• (A) a first artificial RNA molecule comprising a first coding region encoding a norovirus GII.4 VP1 polypeptide at least 90% identical to SEQ ID NO:
• 2358, wherein the first coding region comprises a RNA sequence at least 85% identical to SEQ ID NO:
• 39717;
• (B) a second artificial RNA molecule comprising a second coding region encoding a norovirus GI VP1 polypeptide;
• and
• (C) a third artificial RNA molecule comprising a third coding region encoding a norovirus VP1 polypeptide,
• wherein said at least three artificial RNA molecules each comprise, from 5′ to 3′, (i) a 5′ Cap structure, (ii) a 5′ untranslated region (UTR);
• (iii) the coding region;
• (iv) a 3′ UTR;
• and (v) a Poly(A) sequence of 10 to 200 consecutive adenosines nucleotides,
• wherein said at least three artificial RNA molecules are complexed with a cationic or polycationic compound,
• wherein the pharmaceutical composition is administered to the mammalian subject by intramuscular or intradermal injection.

A method of producing a pharmaceutical composition comprising:

• (I) obtaining at least three artificial RNA molecules comprising:
• (A) a first artificial RNA molecule comprising a first coding region encoding a norovirus GII.4 VP1 polypeptide at least 90% identical to SEQ ID NO:
• 2358, wherein the first coding region comprises a RNA sequence at least 85% identical to SEQ ID NO:
• 39717;
• (B) a second artificial RNA molecule comprising a second coding region encoding a norovirus GI VP1 polypeptide;
• and
• (C) a third artificial RNA molecule comprising a third coding region encoding a norovirus VP1 polypeptide,
• wherein said at least three artificial RNA molecules each comprise, from 5′ to 3′, (i) a 5′ Cap structure, (ii) a 5′ untranslated region (UTR);
• (iii) the coding region;
• (iv) a 3′ UTR;
• and (v) a Poly(A) sequence, and
• (II) formulating said at least three artificial RNA molecules in a pharmaceutically acceptable carrier to produce the pharmaceutical composition.

A method of producing a pharmaceutical composition comprising:

• (I) obtaining a first artificial RNA molecule comprising a first coding region encoding a norovirus GII.4 VP1 polypeptide at least 90% identical to SEQ ID NO:
• 2358, wherein the first coding region comprises a RNA sequence at least 85% identical to SEQ ID NO:
• 39717, wherein said first artificial RNA molecule comprises, from 5′ to 3′, (i) a 5′ Cap structure, (ii) a 5′ untranslated region (UTR);
• (iii) the first coding region;
• (iv) a 3′ UTR;
• and (v) a Poly(A) sequence, and
• (II) formulating said first artificial RNA molecule in a pharmaceutically acceptable carrier to produce a first pharmaceutical composition.