Abstract: A method of providing a therapeutic effect in a human patient which comprises administering to the patient CD34+ cells obtained from cord blood. The CD34+ cells have been engineered with at least one nucleic acid sequence encoding a therapeutic agent. Such CD34+ cells may be engineered by transducing the cells with a retroviral vector including the nucleic acid sequence encoding the therapeutic agent. This method has been applied in treating newborn infants suffering from ADA deficiency.

Abstract: The invention concerns a new method of detecting a rare product of a directed genetic alteration of a cultured cell. The method is applicable to any method of making the alteration provided that a pair of closely linked alterations can be made. The method consists of sequentially using allele specific polymerase chain reaction (PCR) to preferentially amplify sequences containing one of the two linked alterations coupled with a second method that detects the second change in the PCR product. The second method can be restriction digestion, traditional sequencing or pyro-sequencing. Experiments indicate that alterations as rare as one correctly altered copy in 10,000 cells can be detected.

Abstract: A vector, in particular a retroviral vector, which includes a heterologous or foreign gene and a gene encoding a negative selective marker. The negative selective marker enables one to kill cells which contain the gene encoding the negative selective marker, when a particular agent is administered to such cells.

Abstract: The invention concerns a new method of detecting a rare product of a directed genetic alteration of a cultured cell. The method is applicable to any method of making the alteration provided that a pair of closely linked alterations can be made. The method consists of sequentially using allele specific polymerase chain reaction (PCR) to preferentially amplify sequences containing one of the two linked alterations coupled with a second method that detects the second change in the PCR product. The second method can be restriction digestion, traditional sequencing or pyro-sequencing. Experiments indicate that alterations as rare as one correctly altered copy in 10,000 cells can be detected.

Abstract: A method for generating cattle resistant to Bovine Spongioform Encephalopathy through targeted alterations in the PrP gene is disclosed. The PrP gene of a cultured cells is altered to prevent its translation or to encode a dominant disease-resistant form of the protein, and the nucleus of the altered cell is used to clone a founder animal. In one embodiment, a single-stranded DNA fragment containing the alteration is used in single-stranded short fragment homologous replacement to alter the PrP gene.

Abstract: Primary human cells which are genetically engineered with DNA (RNA) encoding a marker or therapeutic which is expressed to be expressed in vivo. Such engineered cells may be used in gene therapy.

Abstract: The present invention provides chimeric primary viruses, which are capable of producing secondary viruses in a producer host cell, and methods of making the same.

Abstract: A method for treating an tumor involves the initial identification of the tumor as one displaying a "bystander effect," whereby in vivo transfer of a gene conferring sensitivity to chemotherapeutic agent affects both transformed and non-transformed tumor cells. Into a tumor thus characterized is introduced in situ a retroviral vector containing the sensitizing gene. The retroviral vector, which may replication-defective or replication-competent, can be introduced directly (if it is replication-competent) or can be provided by means of a packaging cell line. Treatment of the patient with the chemotherapeutic agent thereafter effects tumor regression when as few as 10% of tumor cells are transformed, while normal tissue is not damaged. The anti-tumor impact of the treatment can be increased when the transducing vector also encodes an immune response-enhance substance such as IL-2 or another cytokine.

Abstract: A vector, in particular a retroviral vector, which includes a heterologous or foreign gene and a gene encoding a negative selective marker. The negative selective marker enables one to kill cells which contain the gene encoding the negative selective marker, when a particular agent is administered to such cells.

Abstract: The present invention relates to a system comprising a modified bacterial gene for cytosine deaminase that has been engineered into a eukaryotic expression vector and the expression of the gene by mammalian cells.The present invention further relates to methods, gene therapies and vaccines that employ the negative selectable marker, cytosine deaminase, which has the ability to produce a toxic antimetabolic 5-fluorouracil from 5-fluorocytosine.

Abstract: Primary human cells which are genetically engineered with DNA (RNA) encoding a marker or therapeutic which is expressed to be expressed in vivo. Such engineered cells may be used in gene therapy.

Abstract: The present invention relates to a system comprising a modified bacterial gene for cytosine deaminase that has been engineered into a eukaryotic expression vector and the expression of the gene by mammalian cells.The present invention further relates to methods, gene therapies and vaccines that employ the negative selectable marker, cytosine deaminase, which has the ability to produce a toxic antimetabolite 5-fluorouracil from 5-fluorocytosine.

Abstract: The invention is a method of modulating or controlling autoimmune disease in a host. The method includes the step of administering to the diseased host a pharmaceutical effective amount of succinylacetone. The pharmaceutically effective amount of succinylacetone is desirably infused by an osmotic minipump in order to modulate the effects of autoimmune disease in the host.

Abstract: A method is disclosed for preventing graft rejection of transplanted solid organs, in mammal recipients thereof, by administering an effective graft rejection preventative amount of succinylacetone to said mammals.

Abstract: Primary human cells which are genetically engineered with DNA (RNA) encoding a marker or therapeutic which is expressed to be expressed in vivo. Such engineered cells may be used in gene therapy.