Fingering single genes A zinc finger transcription factor may be useful in gene therapy and cancer
treatment By Cathy Holding
The ability to control in vivo gene expression may be a powerful tool in cancer therapy, gene
therapy of inherited genetic diseases, and for the study of gene function. Small interfering RNAs
are increasingly used in the study of the effects of gene knockout, but these molecules may be of
limited therapeutic use in the clinical setting. In the September 22 PNAS, Siyuan Tan and colleagues
at Sangamo BioSciences, Inc. report the successful use of an engineered zinc finger transcription
factor to completely inhibit specific single gene expression in vivo, providing a model for the
modulation of gene expression that would be of use in both therapeutic and research environments
(PNAS, DOI:10.1073_pnas.2035056100, September 22,
2003).
Tan et al. built upon previous research that linked three two-zinc-finger domains in an engineered
transcription factor to provide specific binding to a unique 18-bp region in the promoter of the
checkpoint kinase 2 (CHK2) gene. This sequence was combined with a maltose-binding protein DNA for
affinity purification of the expressed protein, and the engineered DNA was incorporated into a
repression domain construct for transient expression studies in cell lines or into a self-
inactivating retroviral vector for production of stable cell lines. Expression of the zinc-finger
protein transcription factor (ZFP-TF) was monitored by reverse transcriptase polymerase chain
reaction, microarray analysis, or Western blotting. The authors observed that abolition of
expression of CHK2 was complete and specific by these three criteria and that expression of the ZFP-
TF was constitutive and stable.
Read the rest at 'The Scientist.com' biomedcentral.com03Open ↗
Matter of the heart Adult rat heart stem cells differentiate into cardiac myocytes and repair
injured tissue By Andrea Rinaldi
The prospect of improved regeneration or replacement of damaged tissues and organs is the main goal
of stem cell research. Embryonic stem cells have been the focus of intense study in the past 2
decades, but the biology of the adult stem cells that persevere in mature tissues has been poorly
understood. The presumption that adult tissues, such as the central nervous system, have low or no
self-renewal potential has been challenged by the observation that these tissues host small groups
of resident stem cells that may proliferate and repopulate injured areas. In the September 19 Cell,
Antonio Beltrami and colleagues at the New York Medical College report that heart also contains
adult stem cells, identifying rat myocytes having the properties of cardiac stem cells (Cell, 114:763-
776, September 19, 2003).
Comment: I wonder what role these stem cells might play in cancer? Could stem cells like these
mediate variation in an animal eg if there was some switch to allow a mutation to selectively occur
in response to some environmental condition? The mind boggles.
Kind Regards, Robert Karl Stonjek.