Provided herein are delivery particle systems (XDP) useful for the delivery of payloads of any type. In some embodiments, a XDP particle system with tropism for target cells of interest is used to deliver CRISPR/Cas polypeptides (e.g., CasX proteins) and guide nucleic acids (gNA), for the modification of nucleic acids in target cells. Also provided are methods of making and using such XDP to modify the nucleic acids in such cells.

The disclosure relates to nucleic acids mosaic clade M HIV-1 Env polypeptides and to compositions and vectors comprising same. The nucleic acids are suitable for use in inducing an immune response to HIV-1 in a human.

Recombinant antibody-based molecules that trigger both T-cell and B-cell immune responses are disclosed. The recombinant molecules are comprised by at least one targeting unit and at least one antigenic unit connected through a dimerization motif. Also disclosed are nucleic acid molecules encoding the recombinant antibody-based molecule and methods of treating multiple myeloma or lymphoma in a patient using the recombinant antibody-based molecules or the nucleic acid molecules.

Disclosed are yeast-based immunotherapeutic compositions, human immunodeficiency virus (HIV) antigens, and fusion proteins for the treatment and/or prevention of HIV infection and symptoms thereof, as well as methods of using the yeast-based immunotherapeutic compositions, HIV antigens, and fusion proteins for the prophylactic and/or therapeutic treatment of HIV and/or symptoms thereof.

In certain aspects the invention provides HIV-1 immunogens, including envelopes (CH505) and selections therefrom, and methods for swami immunizations using combinations of HIV-1 envelopes.

HIV-1 Env ectodomain trimers stabilized in a prefusion mature closed conformation and methods of their use and production are disclosed. In several embodiments, the HIV-1 Env ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject. In additional embodiments, the therapeutically effective amount of the HIV-1 Env ectodomain trimers can be administered to a subject in a method of treating or preventing HIV-1 infection.

Provided herein are new compositions and methods for use in introducing transgenes into cells. The compositions are non-viral but achieve levels of transgene integration comparable to those obtained with viral-mediated methods, and can be used for targeted integration of a transgene at a specific genomic locus.

Disclosed herein are trimeric polypeptide pharmaceutical compositions comprising three monomers, each monomer comprising a polypeptide having the amino acid sequence of the N-terminal heptad repeat (NHR or HR1) or C-terminal heptad repeat (CHR or HR2) of the transmembrane glycoprotein of human immunodeficiency virus (HIV) and a trimerization motif.

A method, system, and apparatus for treating a patient with HIV. A vector can be modified from a thymidine kinase gene. The modified vector is expressed in the presence of tat RNA. The modified vector is then package and delivered to HIV-infected cells. The replication of HIV is inhibited by eliminating infected cells in the presence of Ganciclovir. Modified cells are then selected utilizing transient tat RNA transfection and GFP expression. Vector-modified stem cells are then selected for transplantation back into the patient, thereby producing a normal immune system in the patient when the modified vector remains dormant in the absence of HIV tat.

A nucleic acid constructs are used in improving site-specific insertion of an exogenous nucleic acid into a genome. In some aspects the nucleic acid construct having a first polynucleotide sequence encoding a DNA binding protein engineered to bind to a specific genomic DNA sequence, a second polynucleotide having a modified integrase or a modified transposase that enables insertion of exogenous nucleic acid into the genome, and a nucleic acid sequence encoding a linker between the two nucleotides. In some aspects, the nucleic acid construct encodes a fusion protein, for example, a fusion protein for delivery to a cell by a lentiviral particle.