Home > BIOTECHNOLOGY > Antisense therapy

Antisense therapy



Antisense therapy is a form of treatment for genetic disorders or infections. When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid (DNA, RNA or a chemical analogue) that will bind to the messenger RNA (mRNA) produced by that gene and inactivate it, effectively turning that gene “off”. Antisense Therapy is not strictly a form of gene therapy, but is a genetically-mediated therapy and is often considered together with other methods. 

                            The aim of antisense oligonucleotide therapy is to control, and in some cases prevent, the absorption or translation of proteins that are believed to be playing a role in the development of the malignancy. By effectively using this type of therapy to remove essential building blocks used by the cancer, there is an increased chance that various treatments currently used to kill cancer cells will be effective. Antisense therapies of this type work by locking onto the proteins and essentially encasing them. Once encased, the proteins cannot be absorbed and thus cannot feed the cancer. The encased proteins pass through the body without ever contributing to the strength or the further development of the malignant tumor.
Mode of Action
                      At present, the main focus of antisense therapy in oncology involves the use of approximately 20 nucleotides (oligonucleotide) synthesized to be complementary to the specific “sense” (5’ to 3’orientation) mRNA sequence responsible for coding of the targeted protein. Some of the more well-known proteins currently being targeted with antisense agents in development are Bcl-2, H-ras and PKC-Alpha. These proteins, as well as several others presently under investigation, have been implicated in playing a role in the development, growth, and/or maintenance of several types of cancer and tend to be involved in messaging systems involving anti-apoptotic signaling and/or unregulated cellular proliferation
Once introduced into a cell, the “antisense” oligonucleotide hybridizes to the corresponding mRNA sequence through Watson-Crick binding, forming a heteroduplex. Once the duplex is formed, translation of the protein coded by the sequence of bound mRNA is inhibited. There are several mechanisms through which the oligonucleotide/mRNA duplex may hinder subsequent translation. The most widely accepted explanation for several different antisense agents involves the degradation of the mRNA in the heteroduplex by the ubiquitous enzyme Rnase H.
                     Rnase H is attracted to the heteroduplex and cleaves the bound mRNA, while leaving the oligonucleotide sequence intact, allowing the oligonucleotide to continue seeking and binding to corresponding mRNA sequences. Some other accepted explanations of translation inhibition through antisense therapy which may occur separately or in conjunction with Rnase H activity include, but are not limited to, the blocking of appropriate ribosome assembly that disables the ribosomal complexes’ ability to translate, blocking of RNA splicing and/or impeding appropriate exportation of mRNA.
Applications:
Antisense gene therapy also has great potential to lead to responses that last longer than other treatment methods. This is important not only in containing the spread of the cancer, but also in weakening the malignancy and inhibiting the chances of long term damage to vital organs.
Antisense drugs are being researched to treat cancers (including lung cancer, colorectal carcinoma, pancreatic carcinoma, malignant glioma and malignant melanoma), diabetes, ALS, Duchenne muscular dystrophy and diseases such as asthma and arthritis with an inflammatory component.
Antisense therapy is much easier to focus than many other traditional approaches to cancer treatment. The binding action can be controlled, measured for reactions or responses and then redirected as necessary.

Advertisements
Categories: BIOTECHNOLOGY
  1. No comments yet.
  1. No trackbacks yet.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: