The present disclosure relates to a viral gene delivery vector particle and a bispecific polypeptide configured to bind a viral gene delivery vector particle and target cell-specific receptor protein. The disclosure also relates to gene delivery systems, compositions, and methods of use thereof.

The present invention relates generally to methods and compositions for gene therapy and immunotherapy that activate gamma delta T-cells, and in particular, can be used in the treatment of various cancers and infectious diseases.

Polymer-encapsulated viral vector nanoparticles and methods of using them provide enhanced delivery of genetic material for use in gene therapy and other applications. The nanoparticles include an outer shell containing an oligopeptide-modified poly(beta-amino ester) polymer which encapsulates the vector and allows the vector to transduce cells without the need for pseudotyping or the inclusion of any viral fusion protein, such as VSV-G. The polymer-encapsulated vector nanoparticles have a natural tropism for peripheral blood cells, such as leucocytes, without the need for a targeting moiety, and have an improved safety profile compared to pseudotyped viral vectors.

The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

The present invention relates to pseudotyped retrovirus-like particles or retroviral vectors comprising both engineered envelope glycoproteins derived from a virus of the Paramyxoviridae family fused to a cell targeting domain and fused to a functional domain. The present invention also relates to the use of said pseudotyped retrovirus-like particles or retroviral vectors to selectively modulate the activity of specific subsets of cells, in particular of specific immune cells. These pseudotyped retrovirus-like particles or retroviral vectors are particularly useful for gene therapy, immune therapy and/or vaccination.

Disclosed herein are compositions of retroviruses and methods of using the same for gene delivery to a hematopoietic stem cell (HSC), wherein the retroviruses comprise a viral envelope protein comprising at least one mutation that diminishes its native function, a non-viral membrane-bound protein comprising a membrane-bound domain and an extracellular targeting domain.

The disclosure relates generally to the field of T-cell receptors or T-cell receptor mimics, and methods for obtaining novel T-cell receptors or novel T-cell receptor mimics. The compositions and methods described identify pairs of T-cell receptors and antigens. The compositions and methods allow high throughput analysis so that many antigens can be paired with a large repertoire of T-cell receptors.

Promoter sequences for use in expressing a transgene in CD3+ cells are provided. The promoter sequences can be inserted into a vector in a 5′ untranslated region proximal to a transgene. The promoters are selective for expression in CD3+ cells and contain binding sites for transcription factors found in CD3+ cells. The promoters can be integrated into vectors, including polymer-encapsulated lentiviral vector nanoparticles, used to transduce T-cells for genetic immunotherapy to treat cancer and infectious diseases. The T-cell selectivity of the promoters adds an improved safety factor to the use of viral vectors for immunotherapy in vitro and in vivo.

Viral vectors, lentiviral particles, and modified cells are disclosed. They encode or express a small RNA capable of targeting the KIF11 gene. In embodiments, the viral vectors and lentiviral particles further comprise and a KIF11 gene whose non-coding region has been modified such that it is resistant to activity by the small RNA.

The invention provides improved gene therapy vectors, compositions, and methods.