- Antisense therapy
Antisense therapy is a form of treatment for
genetic disorders or infections.When the genetic sequence of a particular geneis known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid( DNA, RNAor a chemical analogue) that will bind to the messenger RNA(mRNA) produced by that gene and inactivate it, effectively turning that gene "off". This is because mRNA has to be single stranded for it to be translated. Alternatively, the strand might be targeted to bind a splicing site on pre-mRNA and modify the exoncontent of an mRNA [cite journal | last = Morcos | first = PA | year = 2007 | title = Achieving targeted and quantifiable alteration of mRNA splicing with Morpholino oligos | journal = Biochem Biophys Res Commun | volume = 358 | issue = 2 | pages = 521–7 | pmid = 17493584 |doi=10.1016/j.bbrc.2007.04.172] .
This synthesized nucleic acid is termed an "anti-sense"
oligonucleotidebecause its base sequence is complementary to the gene's messenger RNA (mRNA), which is called the "sense" sequence (so that a sense segment of mRNA " 5'-AAGGUC-3' " would be blocked by the anti-sense mRNA segment " 3'-UUCCAG-5' ").
Antisense drugs are being researched to treat cancers (including
lung cancer, colorectal carcinoma, pancreatic carcinoma, malignant gliomaand malignant melanoma), diabetes, ALS, Duchenne muscular dystrophy and diseases such as asthmaand arthritiswith an inflammatorycomponent. Most potential therapies have not yet produced significant clinical results, though one antisense drug, fomivirsen(marketed as Vitravene), has been approved by the US Food and Drug Administration(FDA) as a treatment for cytomegalovirus retinitis.
In early 2006, scientists studying the
Ebolavirus at USAMRIIDannounced a 75% recovery rate after infecting four rhesus monkeys and then treating them with an antisense Morpholinodrug (the usual mortality ratefor monkeys infected with Ebola is 100%). [http://www.usamriid.army.mil/press%20releases/warfield_press_release.pdf]
Also in 2006, German physicians reported on a dose-escalation study for the compound AP 12009 (a phosphorothioate antisense oligodeoxynucleotide specific for the mRNA of human transforming growth factor TGF-beta2) in patients with high grade
gliomas. At the time of the report, the median overall survival had not been obtained and the authors hinted at a potential cure. [ [http://meeting.jco.org/cgi/content/abstract/24/18_suppl/1566 Results of G004, a phase IIb actively controlled clinical trial with the TGF-b2 targeted compound AP 12009 for recurrent anaplastic astrocytoma - Hau et al. 24 (18 Supplement): 1566 - ASCO Meeting Abstracts ] ]
ReferencesWeiss, B. (ed.): Antisense Oligodeoxynucleotides and Antisense RNA : Novel Pharmacological and Therapeutic Agents, CRC Press, Boca Raton, FL, 1997
Weiss, B., Davidkova, G., and Zhou, L-W.: Antisense RNA gene therapy for studying and modulating biological processes. Cell. Mol. Life Sci., 55:334-358, 1999
Peptide nucleic acid
* Locked Nucleic Acid
* [http://www.rxlist.com/cgi/generic2/fomivirsen.htm Vitravene Injection Information] , from RXlist.com
* [http://www.antisense-pharma.de/technology/f_technology.htm Antisense Pharma]
* [http://www.medicalnewstoday.com/medicalnews.php?newsid=74957 Antisense Pharma: Promising Phase IIb Results Of Targeted Therapy With AP 12009 In Recurrent Anaplastic Astrocytoma]
Wikimedia Foundation. 2010.
Look at other dictionaries:
antisense therapy — The in vivo treatment of a genetic disease by blocking translation of a protein with a DNA or an RNA sequence that is complementary to a specific mRNA … Glossary of Biotechnology
Antisense RNA — (aRNA) is single stranded RNA that is complementary to a messenger RNA (mRNA) strand transcribed within a cell. Antisense RNA may be introduced into a cell to inhibit translation of a complementary mRNA by base pairing to it and physically… … Wikipedia
antisense — See a. DNA, a. RNA. * * * an·ti·sense an .tī .sens, an ti adj having a sequence complementary to a segment of genetic material specif of, being, relating to, or possessing a sequence of DNA or RNA that is complementary to and pairs with a… … Medical dictionary
therapy — 1. The treatment of disease or disorder by any method. SEE ALSO: therapeutics. 2. In psychiatry, and clinical psychology, a short term for psychotherapy. SEE ALSO: psychotherapy … Medical dictionary
antisense — ˌ adjective Etymology: anti (I) + sense (as in nonsense herein) : having a sequence complementary to a segment of genetic material ; specifically : of, being, relating to, or possessing a sequence of DNA or RNA that is complementary to and pairs… … Useful english dictionary
antisense — adjective Etymology: anti + nonsense Date: 1977 having a sequence complementary to a segment of genetic material; specifically of, being, relating to, or possessing a sequence of DNA or RNA that is complementary to and pairs with a specific… … New Collegiate Dictionary
antisense gene — /æntiˈsɛns dʒin/ (say antee sens jeen) noun a piece of DNA that is complementary to an existing gene which, when inserted into the genome, locks the expression of the primary gene; used in gene therapy … Australian English dictionary
Gene therapy — using an Adenovirus vector. A new gene is inserted into an adenovirull. If the treatment is successful, the new gene will make a functional protein. Gene therapy is the insertion, alteration, or removal of genes within an individual s cells and… … Wikipedia
Pharmacological gene therapy — is a new field that combines pharmacological therapy and gene therapy. It is used either to prevent a defective gene from producing its protein or to increase the concentration of normal protein produced in the body by insertion of DNA or RNA… … Wikipedia
Sense (molecular biology) — In molecular biology and genetics, sense is a concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules. Depending on the context within molecular biology, sense may have slightly… … Wikipedia