Fomivirsen (brand name Vitravene) is an
antisense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context ...
antiviral drug that was used in the treatment of
cytomegalovirus retinitis
Cytomegalovirus retinitis, also known as CMV retinitis, is an inflammation of the retina of the eye that can lead to blindness. Caused by human cytomegalovirus, it occurs predominantly in people whose immune system has been compromised, 15-40% of ...
(CMV) in
immunocompromised
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
patients, including those with
AIDS. It was administered via intraocular injection.
It was discovered at the NIH and was licensed and initially
developed by
Isis Pharmaceuticals, which subsequently licensed it to
Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
.
It was licensed by the FDA for CMV in Aug 1998, and was the first antisense drug that was approved.
Novartis withdrew the marketing authorization in the EU in 2002 and in the US in 2006.
The drug was withdrawn because while there was a high unmet need for drugs to treat CMV when the drug was initially discovered and developed due to the CMV arising in people with
AIDS, the development of
HAART
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multip ...
dramatically reduced the number of cases of CMV.
[
It is an ]antisense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context ...
oligonucleotide
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids ...
-- a synthetic 21 member oligonucleotide
Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids ...
with phosphorothioate Thiophosphates (or phosphorothioates, PS) are chemical compounds and anions with the general chemical formula (''x'' = 0, 1, 2, or 3) and related derivatives where organic groups are attached to one or more O or S. Thiophosphates feature tetrahedr ...
linkages (which are resistant to degradation by nucleases) and has the sequence:
* 5'-GCG TTT GCT CTT CTT CTT GCG-3'
translation
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
of viral mRNA by binding to the complementary sequence of the mRNA transcribed from the template segment of a key CMV gene UL123, which encodes the CMV protein IE2. It was the first antisense
In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context ...
antiviral approved by the FDA.
References
Further reading
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External links
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Anti-herpes virus drugs
Antisense RNA
Therapeutic gene modulation
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