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Antisense Technology

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We are going to turn to another topic or subject Antisense technology. Let me talk about the principles.
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There are two steps in the protein synthesis: transcription and translation. Transcription involves the coding of genetic information from DNA to messenger RNA. And messenger RNA must remain single-stranded to be functional. So now if I have an antisense drug or an oligonucleotide, the messenger RNA is a sense sequence and therefore the antisense drug must be complementary to the messenger RNA in order to block it or inactivate it. And because of the blockade by the antisense drug, the protein now cannot be synthesized so that this cancer cell cannot grow. Now the traditional chemotherapy kills the cells after they are grown.
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The antisense drug vector prohibits the cells or the cancer cells from growth, and therefore the antisense technology has a great potential of cancer therapy. The antisense technology is designed to alter the gene expression and therefore it has great potential for cancer therapy. It was actually first used in plants to alter the levels of various degradative enzymes or plant pigment colors. Since antisense technology focuses on preventing gene expression, so again the potential is great for cancer gene therapy or to treat the viral infection. In fact in 1992, the prestigious science magazine named the antisense molecule as its runner-up in the Molecule of the Year award, the second place. The first place being nitric oxide.
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And of course, you do know that nitric oxide actually evolved into the drug of the century which is viagra. And Fire and Mello share the Nobel Prize because of developing antisense technology. Let’s look at one example of plant bioengineering. This is the tobacco flower. It’s a normal tobacco flower. Look at the right-hand side. Through the antisense technology, the flower becomes lighter in color and smaller. And which one do you like? It all depends on the preference of course. But plant bioengineering is taken to alter the gene expression in plants. Let’s look at another example in 1994.
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U.S FDA approved the first genetically modified food so this tomato is not only crash-resistant it ripens late as a matter of fact and this has a good deal of economical values. The first antisense drug was approved in 2002. And that’s used for Cytomegalovirus infection. Cytomegalovirus infection is an opportunistic infection by this virus when the immune system is compromised in the HIV patient and it leads to the blindness of the eye. And all the antisense drugs the generic name ends with “sen” as you probably have noticed. Fomivirsen is administered by directly injection about 300 micrograms into the vitreous chamber. This injection needs to be done by a specialist and ophthalmologist.

The principle behind antisense technology is that an antisense nucleic acid sequence base pairs with its complementary sense RNA strand and prevents it from being translated into a protein. The oligonucleotide must be nontoxic and sufficiently specific so as not to interfere with other cellular functions. Over the years, chemical modifications of antisense oligonucleotides have not only enhanced the specificity and efficacy but also reduced the side effects.

The basic idea of antisense technology: A synthetic oligonucleotide RNA or DNA molecule complementary to a mRNA is introduced into a cell, The oligonucleotide specifically binds to the target mRNA through the exquisite specificity of complementary based pairing The binding forms an RNA dimmer in the cytoplasm and halts protein synthesis

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Pharmacotherapy: Understanding Biotechnology Products
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