Antagomir

Source: Wikipedia, the free encyclopedia.

Antagomirs, also known as anti-miRs, are a class of chemically engineered oligonucleotides designed to silence endogenous microRNAs (also known as miRNAs or miRs).[1][2][3]

Antagomirs are a kind of

phosphorothioate bonds, and cholesterol conjugation on the 3' end.[4]

Mechanism of action

Antagomirs are

mRNA molecule, and the consequent degradation of that mRNA via the RNA-induced silencing complex (RISC). Due to the promiscuity of microRNAs
, each of which regulate multiple mRNAs, antagomirs can potentially affect the expression of many different mRNA molecules besides the desired target.

Blockmirs are similarly engineered molecules which, on the other hand, are designed to have a sequence that is complementary to an

mRNA sequence that is targeted by a microRNA. Upon binding to an untranslated region of an mRNA, blockmirs sterically block microRNAs from binding to the same site. Because blockmirs bind individual mRNAs and not miRNAs, their activity is more predictable than antagomirs' and less likely to cause off-target effects.[5]


Applications

Antagomirs are used as a method to constitutively inhibit the activity of specific miRNAs associated with disease. For example, antagomirs against miR-21 have been successfully used to inhibit fibrosis of heart[6] and lung.[7]

HCV

The primary method for using

tumor suppressor genes, potentially leading to liver cancer. In order to target HCV mRNA specifically (instead of miRNA-122 as a whole), Blockmir technology has been developed to solely target HCV mRNA, thus avoiding any sort of tampering with oncogene expression. This may be achieved by designing a Blockmir that matches seed 1.[citation needed
]

High-density lipoprotein

MicroRNA-33a/b inhibition in mice leads to increased blood high-density lipoprotein (HDL) levels. Abca1 is essential for production of HDL precursors in liver cells. In macrophages, Abca1 excretes cholesterol from oxidized cholesterol-carrying lipoproteins and thus counteracts atherosclerotic plaques. From this, it is hypothesized that microRNA-33 affects HDL via regulation of Abca1. Therefore, in order to target the regulation of Abca1, a blockmir can be developed that specifically binds to Abca1 mRNA molecules, thus blocking its miRNA site and upregulating its expression. Such an application of blockmir technology could lead to overall increased HDL levels.[citation needed]

Insulin signalling

MicroRNA-103/107 inhibition in mice leads to increased insulin sensitivity and signalling[8] It has been previously shown that caveolin-1-deficient mice show insulin resistance. MicroRNA-103/107 inhibition in caveolin-1-deficient mice had no effect on insulin sensitivity and signalling. Thus, microRNA-103/107 may affect insulin sensitivity by targeting caveolin-1.[9]

Ischemia and immunotherapy

The blockmir CD5-2 has been shown to inhibit the interaction between

ischemic injury in mice.[10] The drug has also been shown to enhance T cell infiltration in combination with immunotherapy in mouse models of pancreatic cancer.[11]

References

  1. PMID 21241758
    .
  2. S2CID 4414240
    .
  3. PMID 16540623
    .
  4. ISBN 978-0-12-396967-5
    , retrieved 2022-09-11
  5. ISBN 978-0-12-813679-9
    , retrieved 2022-09-11
  6. S2CID 8911862
    .
  7. PMID 20395557
    .
  8. PMID 723640
    .
  9. S2CID 2060531
    .
  10. PMID 24009229
    .
  11. PMID 28655790
    .
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