Locked nucleic acid (LNA): A modern approach to cancer diagnosis and treatment

Kamali, Mohammad; Salehi, Mohammad Saied; Fatemi, Somayeh; Moradi, Fereshteh; Khoshghiafeh, Azin; Ahmadifard, Mohamadreza

doi:10.1016/j.yexcr.2022.113442

Cited by 18 publications

(8 citation statements)

References 117 publications

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“…The third-generation nucleic acid analogue, Locked Nucleic Acid (LNA), has emerged as a promising tool in molecular medicine and cancer research. As a result of its unique properties, LNAs have a greater binding affinity, sequence specificity, temperature stability, and nuclease resistance ( Kamali et al, 2022 ). Oligonucleotides that contain one or more nucleotide building blocks and have an additional methylene bridge that locks the ribose moiety into either the C3′-endo (beta-D-LNA) or C2′-endo (alpha-L-LNA) conformation are referred to as having locked nucleic acid, or LNA for short.…”

Section: Mirna and Cancer Immune Evasionmentioning

confidence: 99%

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Abdul Manap,

Wisham,

Wong

et al. 2024

Front. Cell Dev. Biol.

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Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system’s monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells’ evasion of the immune system and promoting cancer progression. Additionally, miRNAs also influence metastasis formation, including the establishment of metastatic sites and the transformation of tumor cells into migratory phenotypes. Specifically, dysregulated expression of these genes has been associated with abnormal expression of oncogenes and tumor suppressor genes, thereby facilitating tumor development. This study aims to provide a concise overview of the significance and function of miRNAs in breast cancer, focusing on their involvement as tumor suppressors in the antitumor immune response and as oncogenes in metastasis formation. Furthermore, miRNAs hold tremendous potential as targets for gene therapy due to their ability to modulate specific pathways that can either promote or suppress carcinogenesis. This perspective highlights the latest strategies developed for miRNA-based therapies.

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Section: Mirna and Cancer Immune Evasionmentioning

confidence: 99%

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Abdul Manap,

Wisham,

Wong

et al. 2024

Front. Cell Dev. Biol.

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“…Within the category of LNAs, mixmers include DNA and LNA nucleotides randomly interspersed within the oligonucleotide, while gapmers have two sequences of LNA nucleotides surrounding a DNA sequence within the oligonucleotide [ 115 ]. Gapmers exert their effects primarily through RNAse H activity, causing nucleolytic cleavage to stop translation, while mixmers work by sterically blocking ribosome binding, preventing the addition of the 5′ cap [ 116 ].…”

Section: Modulation Of Signaling Pathways Involved In Liver Iri By Asomentioning

confidence: 99%

“…Similarly, precision medicine approaches incorporating patient-specific genetic profiles and disease characteristics could optimize ASO therapies by selecting appropriate targets and treatment regimens tailored to individual patients. For example, in Familial Amyotrophic Lateral Sclerosis (FALS), which is responsible for up to 15% of ALS cases, the recent use of subpial injections of Adeno-Associated Virus serotype 9 (AAV9)+anti Superoxide Dismutase 1 (SOD1) ASOs prevented the disease in animal models [ 116 ]. Although viral vectors in humans are limited by their immunogenicity, tailoring medical treatments and interventions based on a patient’s genetic makeup, lifestyle, and environment remains a rapidly evolving and promising area of future research studies.…”

Section: Challenges Future Directions and Conclusionmentioning

confidence: 99%

The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect

Yao,

Kasargod,

Chiu

et al. 2024

Antioxidants

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Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) and metabolic diseases of the liver. Antisense oligonucleotides (ASOs) are an emerging class of gene expression modulators that target RNA molecules by Watson–Crick binding specificity, leading to RNA degradation, splicing modulation, and/or translation interference. Here, we review ASO inhibitor/activator strategies to modulate transcription and translation that control the expression of enzymes, transcription factors, and intracellular sensors of DNA damage. Several small-interfering RNA (siRNA) drugs with N-acetyl galactosamine moieties for the liver have recently been approved. Preclinical studies using short-activating RNAs (saRNAs), phosphorodiamidate morpholino oligomers (PMOs), and locked nucleic acids (LNAs) are at the forefront of proof-in-concept therapeutics. Future research targeting intracellular OxS-related pathways in the liver may help realize the promise of precision medicine, revolutionizing the customary approach to caring for and treating individuals afflicted with liver-specific conditions.

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“…A specific example of a modified AMO is Locked Nucleic Acid (LNA). LNAmodified antisense oligonucleotides offer distinct advantages as they exhibit higher thermal stability, greater solubility in aqueous environments, increased metabolic stability, and enhanced affinity to their target miRNA molecules, rendering them well-suited for in vivo delivery [151]. Anti-miRs have sequences that are complementary to the leading strand of the target miRNA.…”

Section: Suppressing Mirnas With Oncogenic Functionmentioning

confidence: 99%

Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer

Pal,

Ojha,

2023

IJMS

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The alarmingly low five-year survival rate for pancreatic cancer presents a global health challenge, contributing to about 7% of all cancer-related deaths. Late-stage diagnosis and high heterogeneity are the biggest hurdles in treating pancreatic cancer. Thus, there is a pressing need to discover novel biomarkers that could help in early detection as well as improve therapeutic strategies. MicroRNAs (miRNAs), a class of short non-coding RNA, have emerged as promising candidates with regard to both diagnostics and therapeutics. Dysregulated miRNAs play pivotal roles in accelerating tumor growth and metastasis, orchestrating tumor microenvironment, and conferring chemoresistance in pancreatic cancer. The differential expression profiles of miRNAs in pancreatic cancer could be utilized to explore novel therapeutic strategies. In this review, we also covered studies on recent advancements in various miRNA-based therapeutics such as restoring miRNAs with a tumor-suppressive function, suppressing miRNA with an oncogenic function, and combination with chemotherapeutic drugs. Despite several challenges in terms of specificity and targeted delivery, miRNA-based therapies hold the potential to revolutionize the treatment of pancreatic cancer by simultaneously targeting multiple signaling pathways.

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Locked nucleic acid (LNA): A modern approach to cancer diagnosis and treatment

Cited by 18 publications

References 117 publications

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect

Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer

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