Methods of preparing stable nucleic acid liquid formulations

A kit for thermostable DNA/RNA condensate formulation, the kit comprising:

• a buffer;
• a polymer salt mix;
• and
• a diluent.

A kit for thermostable DNA/RNA-LNP formulation, the kit comprising:

• a LNP synthesis buffer;
• a LNP dialysis buffer;
• and
• an excipient mix.

A method method for preparing a stable nucleic acid encapsulated lipid nanoparticles (DNA/RNA-LNP) liquid formulation comprising:

• providing a DNA or RNA solution in an LNP synthesis buffer containing at least one nucleic acid stabilizing buffer salt and at least one other nucleic acid stabilizing excipient, the DNA or RNA having an initial concentration;
• synthesizing DNA or RNA encapsulated LNPs based on the DNA or RNA solution and the LNP synthesis buffer, wherein the LNP synthesis buffer is used as the quenching buffer;
• preparing a plurality of formulation product buffers containing at least one nucleic acid stabilizing buffer salt and at least one other nucleic acid stabilizing excipient, wherein the formulation product buffers have a series of concentrations;
• performing buffer exchange for the DNA or RNA encapsulated LNPs using a LNP product formulation buffer without a macromolecular crowding reagent;
• adding a macromolecular crowding agent and at least one nucleic acid stabilizing excipient at the series of concentrations to the DNA/LNP-LNP formulation after buffer exchange;
• and
• forming the stable nucleic acid encapsulated lipid nanoparticle liquid formulation.