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Kamal et al. J Transl Genet Genom 2024;8:162-85 https://dx.doi.org/10.20517/jtgg.2023.55 Page 174

Mipomersen
Mipomersen is a novel therapeutic antisense oligonucleotide agent that has shown promise in addressing
Familial Hypercholesterolemia, a genetic disorder characterized by elevated levels of low-density lipoprotein
cholesterol in the blood. Familial Hypercholesterolemia is often resistant to traditional lipid-lowering
treatments, making the development of alternative approaches crucial. Mipomersen, a 20-mer
phosphorothioate oligonucleotide, functions by inhibiting the production of Apolipoprotein B-100 mRNA,
a key component of low-density lipoprotein particles. Apolipoprotein B-100 is responsible for the structural
integrity of low-density lipoprotein and is directly involved in cholesterol transport. By targeting
Apolipoprotein B-100 mRNA, Mipomersen helps reduce low-density lipoprotein levels, offering a potential
solution for individuals with Familial Hypercholesterolemia who face an increased risk of premature
cardiovascular disease .
[125]
Givosiran
Givosiran represents a groundbreaking siRNA therapeutic approach in the treatment of Acute Hepatic
Porphyria, which is a rare genetic disorder characterized by the impaired synthesis of heme, a crucial
component of hemoglobin. Givosiran, a 21-bp double-stranded siRNA, targets the root cause of the disease
by inhibiting Aminolevulinate Synthase 1 (ALAS1) mRNA, the enzyme responsible for the initial step in
heme synthesis. By reducing ALAS1 activity, Givosiran helps decrease the accumulation of porphyrin
precursors that trigger acute attacks in patients. This RNA interference technology represents a significant
advancement in managing the symptoms of the disease, providing a novel and targeted solution to improve
the quality of life for individuals affected by this challenging condition .
[126]

Miravirsen
Miravirsen represents a groundbreaking advancement in the treatment of Hepatitis C (HCV), a viral
infection affecting the liver. Developed as an antimiR against miR-122, Miravirsen specifically targets and
inhibits miR-122, a host cell microRNA essential for the replication of HCV. MiR-122 plays a crucial role in
the viral life cycle by promoting HCV RNA stability and facilitating its translation. Miravirsen disrupts this
process by binding to miR-122, preventing its interaction with the viral RNA. This innovative approach
effectively suppresses HCV replication, offering a promising therapeutic strategy. Clinical trials have shown
encouraging results, establishing Miravirsen as a potential game-changer in the fight against Hepatitis C,
with the prospect of improving patient outcomes and reducing the global burden of this infectious
[127]
disease .

Remlarsen
Remlarsen is a novel microRNA mimic therapeutic agent that has shown promising results in the treatment
of cutaneous and pulmonary fibrosis. Fibrosis is a condition characterized by the excessive formation of
fibrous connective tissue, leading to scarring and impaired organ function. Cutaneous fibrosis affects the
skin, while pulmonary fibrosis affects the lungs. One key player in the regulation of fibrosis is miR-29b, a
microRNA that acts as a molecular brake on fibrotic processes by inhibiting the expression of pro-fibrotic
genes. Research suggests that Remlarsen works by mimicking the structure of miR-29b, thereby mitigating
fibrosis in both the skin and lungs. This innovative approach offers hope for individuals suffering from
these debilitating conditions, providing a potential breakthrough in the field of fibrotic disease
therapeutics .
[128]
RG-125
RG-125 is a promising therapeutic agent in the context of Non-Alcoholic Fatty Liver Disease, a prevalent
and potentially serious liver condition associated with excessive fat accumulation in the liver. RG-125
operates by targeting miR-103/107, microRNAs implicated in the regulation of lipid metabolism and the