This Article Free upon publication Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giordano, F. J. Search for Related Content PubMed PubMed Citation Articles by Giordano, F. J. Related Collections Angiogenesis Gene regulation Gene therapy Other Vascular biology

(Circulation. 2007;115:1180-1183.)
© 2007 American Heart Association, Inc.

Editorial

Therapeutic Gene Regulation

Targeting Transcription

Frank J. Giordano, MD

From the Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn.

Correspondence to Frank J. Giordano, MD, Cardiovascular Medicine, Yale University School of Medicine, 333 Cedar St, 3FMP, New Haven, CT 06520. E-mail frank.giordano@yale.edu

Key Words: Editorials • angiogenesis • gene therapy • genes • hypoxia • molecular biology • vasculature

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Circulation, Rajagopolan et al¹ report the first clinical results of a gene therapy approach predicated on transcriptional activation of a patient’s own genes. This represents a second-generation gene therapy methodology for cardiovascular disease and is important for a number of reasons. We have witnessed in the past decade the primary sequencing of the human genome.^2,3 One of the initial reactions to this milestone accomplishment was surprise at the relatively small number of definitive genes that are encoded by human DNA. Although the exact number is still uncertain, estimates as low as 23 299 have been made. In comparison, the genome of the worm Caenorhabditis elegans encodes approximately 19 000 genes, and the genome of the common fruit fly encodes approximately 18 000 genes, raising the question of how such significant differences in biological complexity and diversity are engendered by so few genes. A complete set of answers to this question is not currently in our grasp, but some crucial aspects are understood and are relevant to the clinical trial discussed here.

Article p 1234

One manner in which the biological effect of a finite number of genes is amplified is by alternative splicing. This is the process whereby a single gene encodes a number of alternative proteins by simply including or excluding specific exons within the coding sequence of that gene during mRNA transcription and maturation. The number of alternative splice variants that exist as transcriptional products of the human genome is not known, but . . . [Full Text of this Article]

This article has been cited by other articles:

				L. Lei, S. Mason, D. Liu, Y. Huang, C. Marks, R. Hickey, I. S. Jovin, M. Pypaert, R. S. Johnson, and F. J. Giordano Hypoxia-Inducible Factor-Dependent Degeneration, Failure, and Malignant Transformation of the Heart in the Absence of the von Hippel-Lindau Protein Mol. Cell. Biol., June 1, 2008; 28(11): 3790 - 3803. [Abstract] [Full Text] [PDF]