Diabetes
Glucose homeostasis is regulated both systemically by hormones and at the cellular level by ATP status, but the exact way in which these pathways converge is unknown. Seung-Hoi et al. show that the coactivator transducer of regulated CREB activity-2 (TORC2) inhibits gluconeogenesis, and suggest that blocking the phosphorylation and nuclear translocation of TORC2 might be a potential therapeutic strategy against diabetes.
Ageing
Suppression of aging in mice by the hormone Klotho. Kurosu, H. et al. Science 309, 1829–1833 (2005)
A defect in the Klotho gene was recently shown to accelerate ageing in mice, but the underlying mechanism remained unknown. Kurosu et al. show that Klotho is a circulating peptide hormone and that its overexpression blocks insulin action possibly by suppressing phosphorylation of insulin and insulin-like growth factor-1 (IGF1) receptors. As inhibition of insulin signalling is known to be associated with life-span extension, it seems that Klotho could function as an anti-ageing hormone in mammals.
Biotechnology
Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes. Menzella, H. G. et al. Nature Biotechnol. 23, 1171–1176 (2005)
The synthesis of 'unnatural' natural products by altering or replacing individual polyketide synthase (PKS) gene modules is laborious and time-consuming. Menzella et al. present a combinatorial method for producing polyketides in which the facile synthesis and interchange of PKS modules is facilitated by use of a repeated set of flanking restriction sites. They used the method to synthesize 14 modules from eight PKS gene clusters and associated them in 154 bimodular combinations. Almost half of the combinations successfully mediated biosynthesis of a polyketide in Escherichia coli.
Gene therapy
Systemic delivery of genes to tumours in immunocompetent individuals is hindered by non-specificity, vector neutralization and an inability to target the virus directly to tumours. The authors of this paper exploited the fact that T cells circulate freely and accumulate at sites where specific antigens are expressed. Adoptive transfer of T cells loaded with virus was shown to cure established metastatic disease in mice, whereas T cells alone had no effect. Adsorption to cell carriers might therefore enable systemic delivery of viral vectors for a variety of indications that would benefit from gene therapy.
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In Brief. Nat Rev Drug Discov 4, 886 (2005). https://doi.org/10.1038/nrd1884
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DOI: https://doi.org/10.1038/nrd1884