The present invention relates to methods and compositions for enhancing expression from RNA expression vectores. The invention is based upon the observation that reducing the frequency of the dinucleotide CpG and UpA has a significant effect on expression from such vectores. Aspects of the invention include, amongst others, synthetic RNA vectores, virions, cells, methods of producing vaccines and methods of treatment or immunisation.

The present invention relates to a new method for rescuing an influenza virus and a composition therefor. The method comprises providing a host cell stably integrated with and expressing influenza virus PA, PB1, PB2 and NP genes, and introducing an influenza virus rescue system in which a stop codon is introduced into the PA, PB1, PB2 and NP genes respectively into the host cell to achieve virus rescue. The produced virus particles can be used as a live attenuated influenza vaccine, which is characterized in that, since the genes encoding the related proteins are mutated, it has no replication and proliferation ability in human and normal animal cells, and replication and proliferation can be achieved only in the host cells constructed above and it can fully stimulate the body immunity and effectively protect the body while ensuring the safety.

Disclosed is a viral vector comprising (a) a cDNA of a recombinant viral RNA having a sequence of a Borna disease viral genome comprising a disrupted G gene of the Borna disease viral genome and an inserted G gene of an avian bornaviral genome, wherein the cDNA of the recombinant viral RNA has at least an N gene, an X gene, a P gene and an L gene of the Borna disease viral genome in the same order as in the Borna disease viral genome and has an inserted foreign gene; (b) DNAs encoding ribozymes; and (c) a promoter sequence, wherein (b) the DNAs encoding ribozymes are located upstream and downstream of (a) the cDNA of the recombinant viral RNA, and (a) the cDNA of the recombinant viral RNA and (b) the DNAs encoding ribozymes are located downstream of (c) the promoter sequence. The present invention can be used as a gene introduction technique that does not affect a host chromosome and can be suitable for the application in various fields, such as the treatment and prevention of brain and neurological diseases, visualization techniques of nerve cells in the field of neuroscience, etc.

An IL6R block CAR-T transgenic vector for alleviating CRS includes: AmpR sequence containing ampicillin resistance gene (SEQ ID NO: 1); prokaryotic replicon pUC Ori sequence (SEQ ID NO: 2); virus replicon SV40 Ori sequence (SEQ ID NO: 3); eWPRE enhanced posttranscriptional regulatory element of hepatitis B virus (SEQ ID NO: 11); human EF1a promoter (SEQ ID NO: 12); lentiviral packaging cis-elements for lentiviral packaging; humanized single-chain antibody fragment IL6RscFv1 (SEQ ID NO: 21), IL6RscFv2 (SEQ ID NO: 22), or IL6RscFv3 (SEQ ID NO: 23) of human IL6R; IRES ribosome binding sequence (SEQ ID NO: 25); IL6 signal peptide (SEQ ID NO: 26); human antibody Fc segment (SEQ ID NO: 27); and chimeric antigen receptors of the second or third generation CAR for integrating recognition, transmission and initiation. A preparation method of the IL6R block CAR-T transgenic vector and an application thereof in a preparation of drugs for alleviating CRS.

Disclosed is a viral vector comprising (a) a cDNA of a recombinant viral RNA having a sequence of a Borna disease viral genome comprising a disrupted G gene of the Borna disease viral genome and an inserted G gene of an avian bornaviral genome, wherein the cDNA of the recombinant viral RNA has at least an N gene, an X gene, a P gene and an L gene of the Borna disease viral genome in the same order as in the Borna disease viral genome and has an inserted foreign gene; (b) DNAs encoding ribozymes; and (c) a promoter sequence, wherein (b) the DNAs encoding ribozymes are located upstream and downstream of (a) the cDNA of the recombinant viral RNA, and (a) the cDNA of the recombinant viral RNA and (b) the DNAs encoding ribozymes are located downstream of (c) the promoter sequence. The present invention can be used as a gene introduction technique that does not affect a host chromosome and can be suitable for the application in various fields, such as the treatment and prevention of brain and neurological diseases, visualization techniques of nerve cells in the field of neuroscience, etc.

An IL6R block CAR-T transgenic vector for alleviating CRS includes: AmpR sequence containing ampicillin resistance gene (SEQ ID NO: 1); prokaryotic replicon pUC Ori sequence (SEQ ID NO: 2); virus replicon SV40 Ori sequence (SEQ ID NO: 3); eWPRE enhanced posttranscriptional regulatory element of hepatitis B virus (SEQ ID NO: 11); human EF1a promoter (SEQ ID NO: 12); lentiviral packaging cis-elements for lentiviral packaging; humanized single-chain antibody fragment IL6RscFv1 (SEQ ID NO: 21), IL6RscFv2 (SEQ ID NO: 22), or IL6RscFv3 (SEQ ID NO: 23) of human IL6R; IRES ribosome binding sequence (SEQ ID NO: 25); IL6 signal peptide (SEQ ID NO: 26); human antibody Fc segment (SEQ ID NO: 27); and chimeric antigen receptors of the second or third generation CAR for integrating recognition, transmission and initiation. A preparation method of the IL6R block CAR-T transgenic vector and an application thereof in a preparation of drugs for alleviating CRS.

The present invention relates to methods and compositions for enhancing expression from RNA expression vectores. The invention is based upon the observation that reducing the frequency of the dinucleotide CpG and UpA has a significant effect on expression from such vectores. Aspects of the invention include, amongst others, synthetic RNA vectores, virions, cells, methods of producing vaccines and methods of treatment or immunisation.

Disclosed are a bornavirus vector comprising a nucleic acid encoding an antibody or antibody fragment capable of binding to a mutant SOD1 protein, the antibody or antibody fragment comprising a heavy-chain variable region comprising a heavy-chain CDR1 consisting of an amino acid sequence GFSLNTSGMG (SEQ ID NO: 1), a heavy-chain CDR2 consisting of an amino acid sequence IWWDDDK (SEQ ID NO: 2), and a heavy-chain CDR3 consisting of an amino acid sequence ARLGYAMDY (SEQ ID NO: 3), the heavy-chain variable region optionally having 3 or fewer amino acid substitutions, and/or a light-chain variable region comprising a light-chain CDR1 consisting of an amino acid sequence ONVGTN (SEQ ID NO: 4), a light-chain CDR2 consisting of an amino acid sequence SAS, and a light-chain CDR3 consisting of an amino acid sequence QQYYIYPYT (SEQ ID NO: 5), the light-chain variable region optionally having 3 or fewer amino acid substitutions; a recombinant virus comprising RNA encoded by the bornavirus vector; a cell infected with the recombinant virus; and a pharmaceutical composition comprising the cell.

Compositions and method for treating a folate-resistant disease in a subject are disclosed. The methods involve administering to the subject an effective amount of a composition containing a formate. For example, the method can be used to reducing the risk of neural tube defects during pregnancy. The method can also be used to treat other conditions normally treatable by folate supplementation.