Abstract: An improved method for selectively depleting hypoxic cells within the bone marrow is disclosed. The method can be used to enhance engraftment of hematopoietic stem cells (HSCs) in the bone marrow of a host subject. Also disclosed is a method for treating a cancer within the bone marrow of a host subject.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transferring heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication-competant helper virus.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transfering heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication competent helper virus.

Abstract: Novel methods for treating and preventing arthritis, such as rheumatoid arthritis, are disclosed which employ lentiviral gene delivery vectors, including HIV-based lentiviral vectors, to deliver a therapeutic gene to a subject. Lentiviral-based vectors treat arthritis by promoting high-level expression of the transferred therapeutic gene in the target tissue of the subject.

Abstract: Methods for inhibiting angiogenesis using gene therapy are disclosed. Genes encoding PLGF or VEGF-B are delivered to cells e.g., tumor cells, which express VEGF, such that heterodimers of PLGF/VEGF and/or VEGF-B/VEGF are formed within the cells, preferably at a greater ratio than homodimers of VEGF/VEGF. The heterodimers have reduced angiogenic activity compared to VEGF homodimers.

Abstract: Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transfering heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication-competant helper virus.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transfering heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication-competant helper virus.

Abstract: Novel methods of purifying and concentrating viral particles are disclosed for use in gene therapy, vaccines and viral standards preparation and other possible applications involving preparation and purification of viral particles. The viral particles are purified after the addition of a peptide tag to a protein on the surface of the viral particle, e.g., the envelope, coat or cellular membrane proteins. The viral particles are isolated by affinity absorption specific for the peptide tags. Also disclosed are methods of using the isolated viral particles in gene therapy.

Abstract: Novel methods for treating and preventing arthritis, such as rheumatoid arthritis, are disclosed which employ lentiviral gene delivery vectors, including HIV-based lentiviral vectors, to deliver a therapeutic gene to a subject. Lentiviral-based vectors treat arthritis by promoting high-level expression of the transferred therapeutic gene in the target tissue of the subject.

Abstract: Methods for inhibiting angiogenesis using gene therapy are disclosed. Genes encoding PLGF or VEGF-B are delivered to cells e.g., tumor cells, which express VEGF, such that heterodimers of PLGF/VEGF and/or VEGF-B/VEGF are formed within the cells, preferably at a greater ratio than homodimers of VEGF/VEGF. The heterodimers have reduced angiogenic activity compared to VEGF homodimers.

Abstract: Methods and compositions for promoting angiogenesis by delivering angiogenic factors are disclosed. Also disclosed are improved techniques for delivering angiogenic factors, for example, in the treatment of tissue ischemia.

Abstract: Novel retroviral LTRs are disclosed for use in lentiviral gene therapy vectors. The R region of the LTR is derived from a lentivirus, but lacks all or a portion of the lentiviral TAR sequence to increase the safety of the gene therapy vector. The TAR sequence can be replaced by comparable sequences from the R region from a non-lentiviral retrovirus, thereby generating a hybrid lentiviral/non-lentiviral R region which lacks TAR. Also disclosed are gene therapy vectors including the LTRs and methods of using the vectors in lentiviral-based gene therapy.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transfering heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication-competant helper virus.

Abstract: Novel packaging cell lines which produce recombinant retrovirus, free of detectable helper-virus are disclosed. Also disclosed are methods of making the cell lines and methods of producing recombinant retroviruses from the cell lines. Retroviruses produced by the cell lines include lentiviruses, such as HIV, capable of transfering heterologous DNA to a wide range of non-dividing cells. The packaging cells contain at least three vectors which collectively encode retroviral gag, pol, and env proteins, wherein the gag and pol genes are separated, in part, onto two or more different vectors. This is made possible by fusing Vpr or Vpx to pol proteins separated from gag so that the proteins are targeted to assembling virions. Among other advantages, the packaging cells provide the benefit of increased safety when used in human gene therapy by virtually eliminating the possibility of molecular recombination leading to production of replication-competant helper virus.