Isis Pharmaceuticals, Inc. Message Board
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Why pharma Giants wants ISIS? GSK,SANOFI-GENZYME,BIIB, ASTRAZENICA...wants newer antisense molecules..,
GlaxoSmithKline, Genzyme Corporation, Archemix Corp., and Alnylam Pharmaceuticals, Inc want to enter new era of clinical drug developements using antisense technology.
Antisense technology was first effectively used in plants to alter the levels of various degradative enzymes or plant pigments. The technology was rapidly applied to mammalian cells and in 1992 Science named antisense its runner-up in the molecule of the year award.
In principle, antisense technology is supposed to prevent protein production from a targeted gene. The exact mechanism by which this occurs remains uncertain. Proposed mechanisms include triplex formation, blocking RNA splicing, preventing transport of the mRNA antisense complex into the cytoplasm, increasing RNA degradation, or blocking the initiation of translation. Initially, cellular nucleases dramatically reduce the effectiveness of antisense oligonucleotides by rapidly degrading these molecules after administration. These obstacles can be overcome in applications utilizing synthetic oligonucleotides by altering the nature of the phosphodiester bond by replacing an oxygen with sulfur. Such modified oligonucleotides are termed phosphorothionates. Delivery of antisense oligonucleotides into target cells or the cell nucleus has been problematic. The variety of viral and non-viral delivery systems previously discussed are currently being explored to overcome this obstacle. Animals treated with antisense oligonucleotides have had significant side effects, some of which have been lethal. Currently, the most problematic aspect associated with antisense technology revolves around the specificity of their action. In some cases, non-specific antisense sequences, in other words, sequences which do not bind to the targeted gene or RNA, have prevented gene expression to the same degree as their sequence-specific antisense counterparts. This has led to considerable complication in data interpretation and requires detailed and careful data analysis before contemplation of clinical trials. Since antisense technology focuses on preventing gene expression, it has been most widely applied to cancer gene therapy.-
Antisense oligonucleotides (ASO) are becoming more widely accepted as potential therapeutics for
various diseases. Antisense therapy has emerged as an exciting and promising strategy for the
treatment of various diseases. Antisense are different from conventional drugs that are designed to
interact with protein molecule. Antisense drugs have more selective action and they have the potential
to be more effective and less toxic than conventional drugs. Recent clinical trials confirm the ability of
antisense to significantly suppress target-gene expression. Antisense oligonucleotides are usually
highly selective and thus produce fewer adverse effects than conventional therapeutics. Antisense
technology might be a gateway to the treatment of diseases by targeting the expression of genes rather
than permanently altering them. Antisense oligonucleotides can alter target gene expression by binding
to RNA. Once bound, the ASO either disables or induces the degradation of the target RNA. This
technology may be used to treat various conditions including cancer, diabetes, and hypertension, as
well as autoimmune and cardiovascular diseases. ASOs are potentially potent, selective and welltolerated
drugs. The current status and future direction of several antisense drugs that have potential
clinical use in treatment of various diseases are reviewed in latest Academic Journal publication.Sentiment: Strong Buy
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1984 too this day there has been no successful large scale phase 3 antisense drug trial. They have all failed ! Think ! : (
- 2 Replies to darkouttonight
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dark
think!!!! ............. Generation 2.5
boxcarwhillie -
You are the Only Smart person here to say that Novartis had dumped antisense drugs to ISIS.......rest all including GSK, SANOFI, ASTRA-ZENICA , BIOGEN etc etc are STUPIDS.....they are crazy signing agreement with ISIS and that too the Milestone payments in Billion.....
My dear short friend wakeup - New world is awaiting you...Sentiment: Strong Buy
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Antisense therapy, a magic bullet for the treatment of various diseases: Present and future prospectAntisense drugs are a new generation of gene-silencing
therapeutic agents with potential for targeted causal
treatment of as yet incurable diseases. 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". 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 exon content of
an mRNA
This synthesized nucleic acid is termed an "anti-sense"
oligonucleotide because its base sequence is
complementary to the gene's messenger RNA (mRNA),
Abbreviations: ASO, Antisense oligonucleotides; CFTR, cystic
fibrosis transmembrane conductance regulator; ODN, antisense
oligodesoxynucleoties.
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 glioma and malignant melanoma,
diabetes, Duchenne muscular dystrophy and diseases
such as asthma and arthritis with an inflammatory
component (Agrawal et al., 1995; 2000). Some of the
examples of antisense drug like fomivirsen (marketed as
Vitravene), has been approved by the US Food and Drug
Administration (FDA) as a treatment for cytomegalovirus
retinitis. Mipomersen (ISIS 301012) inhibits human
apolipoprotein (apo) B-100 synthesis and lowers
circulating apoB and low-density lipoprotein cholesterol
levels.- 1 Reply to dinepat203
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Read an article : Antisense therapy, a magic bullet for the treatment of various diseases: Present and future prospects
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Mipomersene is nearing the EMA approval -A Major breakthrough underway.
- 1 Reply to dinepat203
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When it hits....ema approval...off she goes!
Sentiment: Strong Buy
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Antisense therapy, a magic bullet for the treatment of various diseases: Present and future prospects
by dinepat203.2 minutes 20 seconds ago.Permalink
.
Antisense drugs are a new generation of gene-silencing
therapeutic agents with potential for targeted causal
treatment of as yet incurable diseases. 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". 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 exon content of
an mRNA
This synthesized nucleic acid is termed an "anti-sense"
oligonucleotide because its base sequence is
complementary to the gene's messenger RNA (mRNA),
Abbreviations: ASO, Antisense oligonucleotides; CFTR, cystic
fibrosis transmembrane conductance regulator; ODN, antisense
oligodesoxynucleoties.
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 glioma and malignant melanoma,
diabetes, Duchenne muscular dystrophy and diseases
such as asthma and arthritis with an inflammatory
component (Agrawal et al., 1995; 2000). Some of the
examples of antisense drug like fomivirsen (marketed as
Vitravene), has been approved by the US Food and Drug
Administration (FDA) as a treatment for cytomegalovirus
retinitis. Mipomersen (ISIS 301012) inhibits human
apolipoprotein (apo) B-100 synthesis and lowers
circulating apoB and low-density lipoprotein cholesterol
levels.
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