Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The engineering of therapeutic human artificial episomal chromosomes, HAECs, requires the development of strategies to deliver large functional self-replicating extrachromosomal DNA in target cells. Members of the herpesviral family are among the largest episomal double-stranded DNA viruses. As model systems of this family of endemic infectious agents, vectors derived from the human herpes 4 Epstein-Barr virus (EBV) were constructed which transferred up to 180 kb of DNA packaged as infectious virions. Such a transduction strategy was based on a non-oncogenic helper-dependent mini-EBV carrying minimal cis elements for latent replication and virus production. After exposure of human B lymphoma and lymphoblastoid cells to mini-EBVs transducing lacZ and human HPRT minigenes, stable cell transformants were selected which carried the delivered multimeric linear DNAs as circular episomes up to 160-180 kb in size. Following transduction of Lesch-Nyhan disease cells with a mini-EBV/HPRT, normal human HPRT function was restored in cells carrying large episomal HPRT minigenes. Direct visualization of the therapeutic mini-EBV by fluorescent in situ hybridization (FISH) on metaphase and interphase nuclei indicated that 99% (556/563) of the transduced mini-EBV DNA was episomal with an average copy number of one to two per nucleus. This system should allow the delivery of large genes in common diseases such as hemophilia A and codelivery of multiple genes in cells from polygenic diseases such as cancer. The extrachromosomal mini-EBV-based strategy offers an alternative to integrative or non-replicating gene therapy infectious vectors, which may be generally applicable to other herpesviruses characterized by different tropisms.
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PMID:Engineering a mini-herpesvirus as a general strategy to transduce up to 180 kb of functional self-replicating human mini-chromosomes. 898 34

Achalasia is an esophageal motility disorder of unknown etiology. Several studies suggest possible herpes or measles virus etiology, but results are inconclusive. The aim of this study was to test whether herpesvirus (HV), measles (MV), or human papilloma virus (HPV) sequences could be detected in myotomy specimens from a wide spectrum of achalasia patients, using the polymerase chain reaction (PCR) technique. Myotomy specimens from 13 achalasia patients, esophagectomy specimens from nine esophageal cancer patients, and autopsy specimens from six fetuses were studied with the PCR technique. Paired oligonucleotide primers of HV (HSV-1 and 2, CMV, EBV, VZV, and HHV-6), MV and HPV sequences and exon 3 of the HPRT gene were used for the PCR DNA amplification. Amplified products were resolved on agarose gels and stained with ethidium bromide. All specimens yielded the appropriate-sized products for exon 3 of the HPRT and viral controls. No amplified products were seen in the achalasia specimens or controls corresponding to any of the virus sequences tested. The absence of HV, MV, and HPV sequences suggests that these viruses are not associated with achalasia but does not exclude the possibility of a previously unidentified virus as a causal agent. Further studies aimed at identifying an unknown viral agent as a cause for achalasia are warranted.
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PMID:Achalasia is not associated with measles or known herpes and human papilloma viruses. 905 10

Stem cells and their progeny constitute a potential resource for replacing damaged tissues or supplying missing functions, but also pose a threat of aberrant behavior, including neoplastic growth or immunopathology. Suicide genes introduced into these cells before transplantation might provide a means of addressing this threat by permitting the ablation of the cells if they subsequently misbehave. Retroviral transduction of the E. coli gpt and herpes thymidine kinase (HSVtk) suicide genes was used to determine the degree to which stem cells could be sensitized to the prodrugs 6-thioxanthine (6TX) and ganciclovir (GCV) respectively, and whether this sensitivity could persist over many cell generations. The ES-E14TG2a murine embryonic stem cell line was rendered sensitive to quantitative ablation at prodrug concentrations well tolerated by untransduced cells (50 microM 6TX, 1 microg/ml GCV). The HSVtk gene also conferred GCV sensitivity on human mesenchymal stem cells and hematopoietic precursors derived from the murine cells, although ablation was not complete. Because ES-E14TG2a cells are deficient in the cellular enzyme HPRT, they are sensitive to hypoxanthine/aminopterin/thymidine (HAT). This property enhanced the persistence of chemosensitivity in gpt-transduced cells by permitting cells that lost 6TX sensitivity to be ablated with HAT.
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PMID:Suicide gene transduction sensitizes murine embryonic and human mesenchymal stem cells to ablation on demand-- a fail-safe protection against cellular misbehavior. 1208 44