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

This disclosure relates to vectors, isolated cells, compositions, and methods for the treatment of critical limb ischemia and associated disorders. One aspect of the disclosure relates to a vector comprising a nucleic acid encoding a 165A isoform VEGF protein and a promoter that regulates expression of the nucleic acid encoding the VEGF.

The invention provides compositions, kits, and methods for inducing growth arrest, differentiation, or senescence of cancer cells that express thymine DNA glycosylase, and treating the cancer accordingly. The methods comprise inhibiting expression or biologic activity of thymine DNA glycosylase in cancer cells. Inhibition of thymine DNA glycosylase in cancer cells may induce the cells to revert to a healthy, non-cancerous phenotype and/or may induce the cells to senesce. Cancer cells include melanoma, lung, prostate, pancreatic, ovarian, brain, colon, recto-sigmoid colon, and breast cancer cells.

The present disclosure relates generally to gene delivery using a chimeric, retroviral-RNA replicon vector particle for increased expression of transgenes in a host cell. In particular, the chimeric vectors described herein can be used in any of a variety of settings including gene therapy and vaccine settings.

In certain embodiments, the present invention provides the use of microRNA (miR)-200a and/or miR-200c to inhibit ossification and bone formation. In certain embodiments, the present invention provides the use of miR-200a inhibitor to stimulate bone regeneration.

D domain (DD) containing polypeptides (DDpp) that specifically bind targets of interest (e.g., BCMA, CD123, CS1, HER2, AFP, and AFP p26) are provided, as are nucleic acids encoding the DDpp, vectors containing the nucleic acids and host cells containing the nucleic acids and vectors. DDpp such as DDpp fusion proteins, are also provided as are methods of making and using the DDpp. Such uses include, but are not limited to diagnostic and therapeutic applications.

The present invention relates to an immune effector cell which expresses a chimeric antigen receptor targeting GPC3 and exogenous IL12. The present invention further provides a pharmaceutical composition containing the immune effector cell and a method for treating tumor, particularly GPC3 positive tumor by using the immune effector cell or the pharmaceutical composition. The immune effector cell in the present invention is effective to an entity tumor cell in vitro, and is outstanding in effect of extinguishing the entity tumor cell in vivo.

Disclosed is a method for delivering a gene into target cells, wherein immune cells are used as a vector for virus packaging and transportation to complete the delivery of biomacromolecules among cells, and thus change original characteristics of the target cells or generate new characteristics in the target cells. The gene delivery system, on one hand, can kill target cells such as tumor cells by utilizing the specificity of immune cells; and on the other hand, can modify genes of cells in a lesion by gene delivery to target cells, to directly kill the target cells.

MAb 9F4 provides heterologous protection against multiple influenza A H5N1 clade viruses, including one of the recently designated subclades, namely 2.3.4, through binding to a novel epitope. The present invention relates to isolated mouse-human chimeric (xi) IgG.sub.1-9F4 and IgA.sub.1-9F4 MAb which retain high degrees of binding and neutralizing activity against influenza H5N1. The invention also relates to methods of production, kits and uses of the chimeric antibodies in the treatment of influenza A subtype H5N1 disease.

An integration-defective retroviral vector transfer cassette lacking a functional polypurine tract (PPT) is provided. Also provided are isolated nucleic acids that include a heterologous nucleotide sequence, one or two retroviral long terminal repeats (LTRs), a packaging signal, a rev responsive element, and a eukaryotic promoter, wherein the nucleic acid lacks a functional PPT; vectors that include the disclosed isolated nucleic acids; recombinant retroviral particles and mRNAs thereof; retroviral vector kits; and methods for producing integration-defective vector particles, achieving gene expression of a nucleotide sequence of interest, and inserting a nucleotide sequence of interest into a host cell genome in a site-specific or non-specific manner.