Artificial genetic polymers against human pathologies

Ivanov, Gleb; Трибулович, В. Г.; Pestov, Nikolay B.; David, Temitope I.; Amoah, Abdul-Saleem; Korneenko, Tatyana V.; Barlev, Nikolai A.

doi:10.1186/s13062-022-00353-7

Cited by 3 publications

(2 citation statements)

References 184 publications

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“…The recently discovered Ulevostinag/MK-1454 [194] demonstrated the importance of phosphorothioate synthesis stereoselectivity [195,196]. The results of the NCT04220866 study are promising.…”

Section: Pharmaceutical Achievements In the Regulation Of The Cgas-st...mentioning

confidence: 97%

At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment

Korneenko,

Pestov,

Nevzorov

et al. 2023

Pharmaceuticals

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The evolutionary conserved DNA-sensing cGAS-STING innate immunity pathway represents one of the most important cytosolic DNA-sensing systems that is activated in response to viral invasion and/or damage to the integrity of the nuclear envelope. The key outcome of this pathway is the production of interferon, which subsequently stimulates the transcription of hundreds of genes. In oncology, the situation is complex because this pathway may serve either anti- or pro-oncogenic roles, depending on context. The prevailing understanding is that when the innate immune response is activated by sensing cytosolic DNA, such as DNA released from ruptured micronuclei, it results in the production of interferon, which attracts cytotoxic cells to destroy tumors. However, in tumor cells that have adjusted to significant chromosomal instability, particularly in relapsed, treatment-resistant cancers, the cGAS–STING pathway often supports cancer progression, fostering the epithelial-to-mesenchymal transition (EMT). Here, we review this intricate pathway in terms of its association with cancer progression, giving special attention to pancreatic ductal adenocarcinoma and gliomas. As the development of new cGAS–STING-modulating small molecules and immunotherapies such as oncolytic viruses involves serious challenges, we highlight several recent fundamental discoveries, such as the proton-channeling function of STING. These discoveries may serve as guiding lights for potential pharmacological advancements.

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Section: Pharmaceutical Achievements In the Regulation Of The Cgas-st...mentioning

confidence: 97%

At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment

Korneenko,

Pestov,

Nevzorov

et al. 2023

Pharmaceuticals

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“…However, the use of oligonucleotides based on natural nucleic acids has its own limitations, including insufficient resistance to enzymatic degradation in biological media caused by the action of nucleases that cleave phosphodiester bonds, low bioavailability, and the joint use of specific delivery systems [2]. To solve these problems and impart the required properties to polymers, the structural unit of natural nucleic acids is subjected to modification, and this subsequently led to the formation of a new direction of research [3].…”

Section: Introductionmentioning

confidence: 99%

A Visual Compendium of Principal Modifications within the Nucleic Acid Sugar Phosphate Backbone

Novikova,

Sagaidak,

Vorona

et al. 2024

Molecules

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Nucleic acid chemistry is a huge research area that has received new impetus due to the recent explosive success of oligonucleotide therapy. In order for an oligonucleotide to become clinically effective, its monomeric parts are subjected to modifications. Although a large number of redesigned natural nucleic acids have been proposed in recent years, the vast majority of them are combinations of simple modifications proposed over the past 50 years. This review is devoted to the main modifications of the sugar phosphate backbone of natural nucleic acids known to date. Here, we propose a systematization of existing knowledge about modifications of nucleic acid monomers and an acceptable classification from the point of view of chemical logic. The visual representation is intended to inspire researchers to create a new type of modification or an original combination of known modifications that will produce unique oligonucleotides with valuable characteristics.

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At the cross-road of cGAS-cGAMP-STING pathway and DNA damage response: implications for cancer progression and treatment

Korneenko,

Pestov,

Nevzorov

et al. 2023

Preprint

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The evolutionary conserved STING-cGAS pathway represents one of the most important cytosolic DNA sensing systems that is activated in response to viral invasion and/or damaged integrity of the nuclear envelope. The key outcome of this pathway is the production of IFN, which subsequently stimulates hundreds of genes. In oncology, the situation is a complex one since this pathway may serve either anti- or pro-oncogenic roles in a context-dependent fashion. The prevailing understanding is that when the innate immune response is activated by sensing cytosolic DNA, such as from ruptured micronuclei, it results in the production of interferon which attracts cytotoxic cells to destroy tumors. However, in tumor cells that have adjusted to significant chromosomal instability, particularly in relapsed, treatment-resistant cancers, the cGAS–STING pathway often supports cancer progression. In these cells, the pathway initiates a non-canonical nuclear factor κB transcriptional response, fostering the epithelial-to-mesenchymal transition (EMT). Here, we review this intricate pathway in conjunction with cancer progression and development of new treatment modalities.

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Artificial genetic polymers against human pathologies

Cited by 3 publications

References 184 publications

At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment

At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment

A Visual Compendium of Principal Modifications within the Nucleic Acid Sugar Phosphate Backbone

At the cross-road of cGAS-cGAMP-STING pathway and DNA damage response: implications for cancer progression and treatment

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