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From Repression Domains to Designer Zinc Finger Proteins: A Novel Strategy of Intracellular Immunization Against HIV

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Tissue-specific gene regulation of eukaryotic organisms is to a large extent mediated by transcription factors that interact with genomic DNA sequences in a sequence-specific manner. The purpose of this synopsis is to put forward the potential of designer zinc finger proteins in treating infections of human immunodeficiency virus (HIV). Artificial transcription factors containing designer zinc finger structures fused to activator or repressor domains have been designated Transcription Response Modifiers (TRMs). The principle of engineering TRMs has been derived from the analysis of human Krüppel-type zinc finger genes and their products. Our research efforts encompass two fascinating features that are displayed by the human Krüppel-type zinc finger protein KOX1: 1) the Krüppel-type zinc finger domains display rules of sequence-specific DNA recognition, and 2) the evolutionarily conserved Krüppel-associated box (KRAB) presents one of the strongest transcriptional repressors identified so far in mammalian organisms. The KRAB repressor activity is postulated to be mediated through corepressor molecules, such as Silencing Mediating Protein-1 (SMP-1). Thus, the structural organization and functional analysis of zinc finger proteins revealed principles of zinc finger transcription factors that are applicable for reducing the viral load in individuals infected with HIV. In this article, a novel concept of generating therapeutic proteins is outlined that might be conceptually promising in modulating gene expressions of any kind.
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Keywords: Activator domains; Designer zinc finger proteins; HIV-1; Krüppel-type zinc finger genes; Repressor domains

Document Type: Research Article

Publication date: January 1, 1996

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  • Gene Expression, The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression, The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.
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