By Abelson J.N., Simon M.I., Phillips I.M. (eds.)
Antisense expertise is the power to control gene expression inside of mammalian cells delivering robust experimental methods for the learn of gene functionality and gene law. for instance, tools that inhibit gene expression enable reviews which probe the traditional functionality of a selected product inside a telephone. Such method can be utilized in lots of disciplines corresponding to pharmacology, oncology, genetics, mobile biology, developmental biology, molecular biology, biochemistry, and neurosciences. This quantity should be a really vital instrument in biomedical-oriented examine. The significantly acclaimed laboratory common for greater than 40 years, tools in Enzymology is without doubt one of the so much hugely revered courses within the box of biochemistry. on the grounds that 1955, each one quantity has been eagerly awaited, often consulted, and praised through researchers and reviewers alike. Now with greater than three hundred volumes (all of them nonetheless in print), the sequence includes a lot fabric nonetheless appropriate this present day - really a vital book for researchers in all fields of lifestyles sciences.
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Extra resources for Antisense Technology: General Methods, Methods of Delivery, and RNA Studies Part A
Phillips, Regul. Pept. 59, 171 (1995). 135M. M. McCarthy, D. A. Nielsen, and D. Goldman, Regul. Pept. 59, 163 (1995). 136A. Osen-Sand, M. Catsicas, J. K. Staple, K. A. Jones, G. Ayala, J. Knowles, G. Grenningloh, and S. Catsicas, Nature 364, 445 (1993). 30 GENERALMETHODS [ 11 Ax receptor has been reported to reduce receptor numbers in the airway smooth muscle and to inhibit adenosine, house dust mite allergen, and histamine-induced bronchoconstriction. 137Neither control nor oligonucleotide complementary to bradykinin B2 receptors reduced the density of adenosine A1 receptors, although the oligonucleotides complementary to bradykin in B2 receptor mRNA reduced the density of these receptors.
Based on our experience to date, we believe that the dose-limiting toxicity in humans will be dotting abnormalities, which will be associated with peak plasma concentrations well in excess of 10/zg/ml. 006 to 10-15 mg/kg, depending on the target, the end point, the organ studied, and the time after a dose when the effect is measured. Thus, it would appear that phosphorothioate oligonucleotides have a therapeutic index that supports their evaluation for a number of therapeutic indications. Conclusions Phosphorothioate oligonucleotides have perhaps outperformed many expectations.
Koretzky, and D. M. Klinman, Nature 374, 546 (1995). , alteration of the activity of growth factors, cytokine release, nonspecific effects on membranes that might trigger arachidonic acid release, or inappropriate intracellular signaling. Presumably, new analogs that deviate significantly more from natural D N A would be even less likely to be integrated. A second concern that has been raised about possible genotoxicity is the risk that oligonucleotides might be degraded to toxic or carcinogenic metabolites.