Antibody based gene therapy with tissue-directed expression
Embodiments of the disclosure include methods and compositions for treatment of a medical condition related to the liver, including at least viral infections and liver cancer, for example. In specific embodiments, immunotherapies are provided for delivering polynucleotides locally to the liver, wherein the polynucleotides encode particular gene products that include bispecific antibodies, including those that target certain liver antigens, for example.
1. A composition comprising a polynucleotide encoding a secretable polypeptide that comprises at least one Hepatitis B surface antigen-binding antibody and at least one immunostimulatory antibody, wherein the composition comprises the same or a different polynucleotide that encodes a cytoprotective agent, wherein the cytoprotective agent is Bcl2, Bcl-XL, Mcl-1, CED-0, Bfl-1, X-linked inhibitor of apoptosis protein (XIAP), c-IAP1, C-IAP2, NAIP, Livin, Survivin, serpin proteinase inhibitor 9, or SERPINB4.
2. The composition of claim 1 , wherein the cytoprotective agent is a nucleic acid or a polypeptide.
3. The composition of claim 2 , wherein the cytoprotective agent is an mRNA that comprises untranslated sequences that are targetable by an miRNA molecule of an individual.
4. A polypeptide having an amino acid sequence selected from SEQ ID NOs: 15-21, 38, 40, 41 and 43.
5. A composition comprising a polynucleotide encoding a secretable polypeptide that comprises at least one Hepatitis B surface antigen-targeting binding antibody and at least one immunostimulatory antibody, wherein said polynucleotide comprises a liver-specific promoter selected from a thyroxine binding globulin (TBG) promoter, an apoE promoter, and an alpha1-antitrypsin promoter, such that it is capable of producing said secretable polypeptide inside liver cells of a mammalian subject without toxicity as compared to an untreated mammalian subject.