The present invention provides an in-vitro method of reducing the efficiency of transducing malignant cells of the blood system of a subject that are not derived from T cells with lentiviral vector particles without reducing the efficiency of transducing T cells in a sample comprising T cells and said malignant cells. A combination of compositions comprising a first composition and a second composition is also disclosed, wherein said first composition comprises i) transduced T cells of a subject, wherein said transduced T cells express a CAR comprising an antigen binding domain, wherein the antigen binding domain of said CAR binds specifically to a tag of a tagged polypeptide, and ii) non-transduced malignant cells of the blood system of said subject, and wherein said second composition comprises said tagged polypeptide, wherein said tagged polypeptide binds specifically to an antigen expressed on the surface of said malignant cells. Alternatively, the transduced T cells of said first composition may comprise a nucleic acid encoding a CAR and an inducible gene expression system, and said second composition may comprise an induction agent inducing said gene system.

Nucleic acid molecules such as shRNA clusters and artificial miRNA clusters are disclosed, Also disclosed are methods of use, compositions, cells, viral particles, and kits relating to the nucleic acid molecules disclosed herein. The disclosure provides, at least in part nucleic acid molecules such as shRNA clusters encoding shRNA-like molecules and artificial miRNA clusters encoding modified pri-miRNA-like molecules. The shRNA clusters and artificial miRNA clusters disclosed herein can be used, for example, to produce artificial RNA molecules, e.g., RNAi molecules. Cells, viral particles, compositions (e.g., pharmaceutical compositions), kits, and methods relating to the nucleic acid molecules, e.g., shRNA clusters and artificial miRNA clusters, are also disclosed. The nucleic acid molecules (e.g., shRNA clusters and artificial miRNA clusters), artificial RNA molecules (e.g., RNAi molecules), cells, viral particles, compositions (e.g., pharmaceutical compositions), and kits and methods disclosed herein can be used to treat or prevent a disease, e.g., HIV infection and/or AIDS.

There are provided compositions and methods for modulating stem cell division, in particular, division symmetry. It has been demonstrated that Wnt7a polypeptide fragments promoting symmetrical expansion of stem cells. The compositions and methods of the invention are useful, for example, in modulating stem cell division symmetry in vitro, ex vivo, and in vivo, in replenishing and expanding the stem cell pool, and in promoting the formation, maintenance, repair and regeneration of tissue.

The present invention provides pharmaceutical compositions of an integration-promoting peptide and hydroxyl halide salts of said peptide. The pharmaceutical compositions of the present invention are stable and maintain the peptide soluble upon administration. Methods of treating viral infection and cancer with the peptide salts and compositions thereof are also provided.

Novel lentivirus packaging systems engineered with a synthetic gene network having a positive feedback loop to amplify the expression of virus genes are provided. When co-transfected into a host cell with a transfer plasmid and envelope vector, extremely high viral titers are achieved when compared to transfection of a host cell with conventional third generation packaging systems. Methods for enhancing production of lentivirus, compositions comprising high titer lentivirus, and therapeutic methods based on delivery of lentiviral nucleic acid to target cells are also provided.

The invention is directed to a system comprising a lentivirus vector particle which encodes at least one guide RNA sequence that is complementary to a first DNA sequence in a host cell genome, a Cas9 protein, and optionally a donor nucleic acid molecule comprising a second DNA sequence. The invention also is directed to a method of altering a DNA sequence in a host cell using such a system, where the host cell can be in a human and the altered DNA can be of the human β-globin gene. The invention also is directed to a fusion protein comprising a Cas9 protein and a cyclophilin A (CypA) protein. The invention also is directed to sequences of vectors that can be used in the system and method.

The present invention provides compositions and methods for transducing cells (e.g. T cells or immune cells). Also provided herein are methods of treating a disease in a subject in need thereof.

Novel lentivirus packaging systems engineered with a synthetic gene network having a positive feedback loop to amplify the expression of virus genes are provided. When co-transfected into a host cell with a transfer plasmid and envelope vector, extremely high viral titers are achieved when compared to transfection of a host cell with conventional third generation packaging systems. Methods for enhancing production of lentivirus, compositions comprising high titer lentivirus, and therapeutic methods based on delivery of lentiviral nucleic acid to target cells are also provided.

A method is provided to enhance repair or regeneration of a mammalian cardiovascular system to include heart and/or vasculature comprising: administering to a mammal in need thereof a composition comprising an effective amount of an agent that elevates levels of Smo, Ptc1, Shh, Ihh, Dhh, Gli1, Gli2, or Mycn.

The present invention provides compositions and methods for transducing cells (e.g. T cells or immune cells). Also provided herein are methods of treating a disease in a subject in need thereof.