1. In the name of god, the compassionate, the merciful Antisense RNA Dr.sharif Moghaddam By: Niloofar Beiranvand

2. Antisense RNA is a single-stranded RNA that is complementary to a messenger RNA (mRNA) strand transcribed within a cell Antisense RNA introduced into a cell to inhibit translation of a complementary mRNA by base pairing to it and creating barrier to the translation machinery. That is physically obstructing of the translation machinery.  What is antisense RNA?

3. An example of naturally occurring mRNA antisense mechanism is the hok/sok system of the E.coli R1 plasmid. This translational arrest causes reduced amount of protein expression. Well-known examples of GM plants produced by this technology: This technique was first used commercially in 1988 for the Flavrsavr tomato. The gene chosen for inactivation was polygalacturonase (PG). The Calgene company created a transgenic tomato plant expressing the antisense RNA.

5.  Role of antisense RNA: To inactivate the polygalacturonase gene. To inactivate ethylene synthesis. Reduction of starch content in vegetables. Modification of flower colour in various decorative plant. Mammalian genomes encode numerous natural antisense transcripts, but the function of these transcripts is not well understood.

6.  Hok/sok system(Natural mechanism): It was the first type toxin- antitoxin pair to be identified. The hok/sok system involves three genes: 1. hok- host killing - a long lived (half-life 20 minutes) toxin. 2.Sok-suppression of killing - a short lived (halflife 30 seconds) RNA antitoxin. 3.Mok-modulation of killing - required for hok translation.

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16.  RNA interference: RNA interference (RNAi) is an evolutionary highly conserved defense mechanism of posttranscriptional gene silencing (PTGS) occurring naturally against double stranded RNA (dsRNA) that causes sequence-specific gene regulation resulting in inhibition of translation or transcriptional repression of mRNA sequences. 16

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18.  Diff. between antisense technology & RNAi: Antisense rna phenomenon, dubbed RNA interference (RNAi) The intended effect in both will be same i.e. gene silencing but the processing is little but different. Antisense technology degrades RNA by enzymes RNaseH while RNAi employed the enzyme DICER to degrade the m RNA. RNAi are twice larger than the antisense oligonucleotide.

19.  Antisense therapy : Antisense therapy is a mode of treatment for genetic disorder or infections. A complementary mRNA strand is synthesized on the basis of the known pathogenic sequence, and which switch ‘off’ the pathogenic gene by activating the degrading enzyme RNaseH. Antisense drugs are being researched to treat cancers, HIV, CMV etc. Formivirsen is the first antisense antiviral drug developed to treat CMV. It was licensed by FDA in Aug, 1998.

20. Cancer– In 2006, a German physician reported the dose escalation of AP compound can be helpful in curing cancer. It is an antisense to the growth factor TGF-beta2. HIV– In feb,2010 Researcher reported successful reducing the viral load of HIV by developing modified T-Cell, which is antisense to the HIV envelope protein.

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