The present invention provides nucleic acid, vectors, viruses, and recombinant cells comprising triple-stranded structures, such as those resulting from central initiation and termination of HIV-1 reverse transcription at the center of HIV-1 linear DNA genomes. These triplex structures can act as a cis-determinant of HIV-1 DNA nuclear import, allowing infection of non-dividing target cells. In one aspect, the presence of the DNA triplex sequence in an HIV vector strongly stimulates gene transfer in hematopoietic stem cells. The invention also provides methods of using these triplex structures for making recombinant cells, as well as methods of using the recombinant cells to express proteins of interest both in vitro and in vivo.

The present invention relates to methods for preparing virus-like particles comprising immunogenic cyclic dinucleotides and its use for treating cancer.

The present invention provides nucleic acid, vectors, viruses, and recombinant cells comprising triple-stranded structures, such as those resulting from central initiation and termination of HIV-1 reverse transcription at the center of HIV-1 linear DNA genomes. These triplex structures can act as a cis-determinant of HIV-1 DNA nuclear import, allowing infection of non-dividing target cells. In one aspect, the presence of the DNA triplex sequence in an HIV vector strongly stimulates gene transfer in hematopoietic stem cells. The invention also provides methods of using these triplex structures for making recombinant cells, as well as methods of using the recombinant cells to express proteins of interest both in vitro and in vivo.

A virus-like particle encapsulating a target protein is provided. The virus-like particle contain a Gag protein, and the Gag protein forms a dimer with the target protein.

Compositions and methods for delivering a protein of interest such as a cell homing molecule (e.g., CXCR4) into host cells (e.g., to hematopoietic cells). The compositions and methods provided herein may be used to enhance homing and long-term engraftment of hematopoietic cells post transplantation.

The present invention relates to a retroviral system for the transfer of non-viral RNA into target cells and more particularly a retroviral particle capable of delivering multiple RNAs. More particularly, it relates to retroviral particles comprising a protein derived from the Gag polyprotein an envelope protein, optionally an integrase and at least two encapsidated non-viral RNAs, the encapsidated non-viral RNAs each comprising an RNA sequence of interest linked to an encapsidation sequence, each encapsidation sequence being recognised by a binding domain introduced into the protein derived from the Gag polyprotein and/or into the integrase.

This disclosure relates to a virus-like particle in which a small molecule-protein complex is entrapped, ensuring the formation of the small molecule-protein complex under physiological conditions, while protecting the small molecule-protein complex during purification and identification. The disclosure further relates to the use of such virus-like particle for the isolation and identification of small molecule-protein complexes.

In one aspect, the invention relates to methods and compositions for determining migration of a virus particle to the nucleus of a cell. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The inventors developed a new system to modify tropism of syncytins, envelope proteins, which can be used to functionalize particles such as virus particle or more particularly viral-like particles (VLPs), and used for gene transfer or other applications. In particular, they created a fusion protein containing the Syncytin-1 (SYN) signal sequence (SS), a targeting moiety (either natural or engineered), the SYN protein and a flexible linker between SYN and the targeting moiety to enhance transduction of the cell type expressing the receptor or the antigen targeted by the targeting moiety, for instance hematopoietic stem progenitor cells (HSPCs). The inventors demonstrated that the fusion strategy allows modification of syncytin tropism towards different receptors in order to target f the desired cell type. The system is adaptable to other desired antigens to retarget the fusion protein to a specific cell type.

The present disclosure provides enveloped delivery vehicles (EDVs) comprising a nucleic acid-binding effector polypeptide, or a nucleic acid encoding the nucleic acid-binding effector polypeptide, where the EDV comprises a fusion polypeptide comprising (i) a viral envelope protein and (ii) a targeting polypeptide that provides for binding to a target cell. The present disclosure provides methods of using an EDV of the present disclosure for delivery of, e.g., a nucleic acid-binding effector polypeptide, to a eukaryotic cell.