The present invention relates to a new vaccine delivery system. In particular, the present invention includes compositions and methods of integrally transformed non-pathogenic, commensal bacteria that can express a nucleic acid molecule of a foreign polypeptide, wherein the nucleic acid molecule that encodes the foreign polypeptide is stably integrated into genomic DNA of the bacteria. The foreign polypeptide includes a vaccine antigen that elicits an immunogenic response, an inhibitor of a pathogen, or an immune booster or modulator.

The present invention describes a unique method of treating cancer with the administration of an improved DAGRS construct which functions as a humanized agent specifically targeting cancer cells in vivo. A specific DAGRS is described constructed of a humanized drug delivery biologic, carboxyl to an Apoptin fragment consisting of Apoptin's proline-rich SH3-binding fragment, a spacer, and a MAP kinase (MAPK) phosphorylation site, in replacement of the SH3-binding domain at HIV-1 TAT's amino terminus. Apoptin is a viral protein with incumbent immunogenicity and toxicity in humans. Improved DAGRS constructs are described that replace the viral VP3 peptide with human AKT peptide or derivative, all equivalently spaced 11 amino acids from the initial proline to the beginning of the MAPK phosphorylation site, through which technology the DAGRS is fully humanized. DAGRS provide for improved bioavailability, enhanced specific activity, and low toxicity for in vivo treatment of cancer. DAGRS are a superior method for targeting any oncogene with an inhibitory peptide.

An algorithm for humanization is described through which human functional equivalent(s) to viral product(s) are identified by alignment of peptides anchored at each end by matching functional motifs that are spaced equivalently distant in the two aligned peptides. The algorithm totally disregards the primary amino acid composition of the spacer, and as such separates from current computer algorithms that prioritize primary amino acid alignments. Accounting for spacing dictates that functional domains be oriented correctly in three dimensions. The invention taught here can be developed into computer algorithms for rapidly identifying these anchored alignments, and thereafter developing safe humanized drugs from disruptive viral activities. Computers once taught the basic rules for anchoring equivalents, can improve on the basic algorithm through artificial intelligence to expand drug development.

The present invention relates to a viral vector for silencing a gene specifically in astrocytes comprising: an astrocyte-specific viral envelope protein, a first nucleic acid sequence encoding a transcription activator and at least one target sequence of a neuron-specific miR under the control of an astrocyte-specific promoter, anda second nucleic acid sequence encoding a RNA for silencing the gene under the control of a promoter inducible by the transcription activator.

Provided are viral particles for activating and transducing immune cells in vitro or in vivo, and compositions and methods for using said viral particles.

Provided for herein are compositions and methods that can be used to transduce cells and deliver genetic information that can then be expressed in the transduced cell. Also provided herein are methods of treating a disease in a subject using the compositions and methods provided.

A pharmaceutical composition includes, as active substance a mutated lentiviral ENV protein, substantially devoid of immunosuppressive properties or a variant of the mutated lentiviral ENV protein or a fragment of the above proteins, in association with a pharmaceutically acceptable carrier.