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 disclosure relates to recombinant rhesus cytomegalovirus (RhCMV) and human cytomegalovirus (HCMV) vectors encoding heterologous antigens, such as pathogen-specific antigens or tumor antigens, which may be used, for example, for the treatment or prevention of infectious disease or cancer. The recombinant RhCMV or HCMV vectors elicit and maintain high level cellular immune responses specific for the heterologous antigen while including deletions in one or more genes essential or augmenting for CMV replication, dissemination or spread.

The subject invention pertains to materials and methods for detecting, preventing and treating retroviral infections in humans and other animals susceptible to infection by retrovirus. It has been discovered that FIV can be transmitted from cats to humans and that the FIV can infect human cells in vivo and that antibodies generated by the infected person cross-react with HIV antigens. Thus, the methods and compositions of the subject invention can be used to detect, prevent and treat FIV infection in humans and other non-feline animals that are susceptible to FIV infection. The methods and compositions of the invention can also be used to prevent and treat infection by HIV in humans.

The present application relates to epitope-targeted SIV and HIV vaccines. The invention provides novel envelope glycoproteins which may be utilized as HIV-1 vaccine immunogens, antigens for crystallization, and for identification of broadly neutralizing antibodies. The invention encompasses preparation and purification of immunogenic compositions which are formulated into vaccines of the present invention.

The invention provides compositions and methods related to conformationally stabilizing primate immunodeficiency virus envelope glycoprotein trimers.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells, in shorter times than previously and/or in whole blood or a component thereof. In some embodiments a lymphodepletion filter assembly is used before or after forming a reaction mixture where lymphocytes are contacted with recombinant retroviral particles in a closed system, to genetically modify the lymphocytes.

Compositions are disclosed that induce broadly HIV theraputic and vaccine inducing antibodies against diverse HIV clades and relate to the ability to identify HIV gp120-derived short peptide sequence immunogens and various therapeutic compositions made from the identified peptides which compose CCR5 binding sites. Also disclosed are methods of selecting peptide sequences that are likely candidates for drugs which will offer effective treatment in such areas as Alzheimer's disease, psoriasis, multiple sclerosis and other diseases associated with the human inflammatory cascade as well as related retroviruses such as HTLV-1, the cause of tropical spastic paraparesis.

In one aspect, the present invention provides recombinant polynucleotides. In some embodiments, the recombinant polynucleotides comprise a cytomegalovirus (CMV) genome, or a portion thereof, and a nucleic acid sequence encoding an antigen, wherein the CMV genome or portion thereof comprises a mutation within a interleukin-10-like gene sequence. Methods for preventing and treating diseases such as infectious diseases and cancer are also provided herein.

The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralizes a wide spectrum of HIV primary isolates and/or to an immunogen that induces a T cell immune response. The invention also relates to a method of inducing anti-HIV antibodies, and/or to a method of inducing a T cell immune response, using such an immunogen. The invention further relates to nucleic acid sequences encoding the present immunogens.

Dry, e.g., lyophilized, polymeric transfection agent compositions are provided. The dry compositions include a polymeric transfection agent and a buffer. In some instances, the compositions further include one or more nucleic acids. Also provided are methods of making and using the compositions, as well as kits including the compositions.