Provided herein are, inter alia, nucleic acids (e.g., siRNA), lipid nanoparticles comprising nucleic acids, pharmaceutical compositions comprising nucleic acids, pharmaceutical compositions comprising lipid nanoparticles, and methods of treating COV-ID-19, SARS viruses, and Middle Eastern respiratory syndrome.

Some aspects of this disclosure provide modified mRNA (modRNA) encoding retinaldehyde dehydrogenase (RALDH) enzyme, in addition to methods of synthesis, administration, use, and treatment. In some embodiments, the modRNA may be used in a vaccine to treat infections (e.g., mucosal infections) and/or cancers (e.g., mucosal cancers).

The invention relates to the field of RNA stabilisation, and more particularly to the use of deuterium oxide (D.sub.2O) during storage and/or synthesis of RNA molecules. Described herein are deuterium-stabilised ribonucleic acid (RNA) molecules that display an increased resistance to thermal and enzymatic hydrolysis. Also described are aqueous compositions comprising stabilized RNA molecules and methods for making same. The invention is particularly useful for in the manufacture of RNA-based therapeutics, such as mRNA vaccines, to render them less sensitive to temperature fluctuations.

The present invention is directed to a polymeric carrier cargo complex, comprising as a cargo at least one nucleic acid (molecule) and disulfide-crosslinked cationic components as a (preferably non-toxic and non-immunogenic) polymeric carrier. The inventive polymeric carrier cargo complex allows for both efficient transfection of nucleic acids into cells in vivo and in vitro and/or for induction of an (innate and/or adaptive) immune response, preferably dependent on the nucleic acid to be transported as a cargo. The present invention also provides, pharmaceutical compositions, particularly vaccines and adjuvants, comprising the inventive polymeric carrier cargo complex and optionally an antigen, as well as the use of such the inventive polymeric carrier cargo complex and optionally an antigen for transfecting a cell, a tissue or an organism, for (gene-)therapeutic purposes as disclosed herein, and/or as an immunostimulating agent or adjuvant, e.g. for eliciting an immune response for the treatment or prophylaxis of diseases as mentioned above. Finally, the invention relates to kits containing the inventive polymeric carrier cargo complex and/or the inventive pharmaceutical composition, adjuvant or vaccine in one or more parts of the kit.

The invention provides SARS-2 spike protein designs and uses thereof.

Disclosed herein, in certain embodiments, are recombinant Arc and endogenous Gag polypeptides, and methods of using recombinant Arc and endogenous Gag polypeptides.

The present invention provides a vaccine composition for use in neurodegenerative diseases and an infectious virus vaccine composition for inducing an antibody recognizing the conformation of antigens. The vaccine composition of the present invention induces the production of an antibody recognizing the conformation of antigens. The antibody recognizing the conformation of antigens has high specificity for an antigen, and thus can be useful for ameliorating, preventing or treating diseases.

The disclosure relates to novel lipidic compounds, lipid nanoparticles (LNPs) containing thereof, and the use of the lipidic compounds or the LNPs for the delivery of nucleic acid. The lipidic compounds as disclosed herein comprise at least one terminal radical of formula (I): *—NH—CX—(NH)n-A (I) wherein: —*- represents a single bond linking said radical of formula (I), directly or not, to to one C.sub.10 to C.sub.55 lipophilic or hydrophobic tail-group; —n is 0 or 1; —X is an oxygen or sulfur atom, and —A represents an optionally substituted 5- or 6-membered unsaturated heterocyclic radical or 5- or 6-membered heteroaromatic ring radical, both containing at least one nitrogen atom; or one of the pharmaceutically acceptable salts of said radical of formula (I); and with said compound that is in all the possible racemic, enantiomeric and diastereoisomeric isomer forms.

The use of anti-HPV immunogens and nucleic acid molecules that encode them for the treatment and prevention of vulvar dysplasia are disclosed. Pharmaceutical composition, recombinant vaccines comprising DNA plasmid and live attenuated vaccines are disclosed as well methods of inducing an immune response to treat or prevent vulvar dysplasia are disclosed.

Methods and compositions of whole cell vaccines for delivering immune modulatory molecules IL-12 and at least one of IL-21 and/or IL-18 to result in a therapeutic effect are disclosed. The methods and compositions use stably integrating lentiviral delivery systems. The methods are useful for therapeutically and prophylactically treating cancer such as leukemia.