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  1. Article ; Online: Inhibition of survivin by 2'-

    Li, Yalin / Chen, Suxiang / Rahimizadeh, Kamal / Zhang, Zhen / Veedu, Rakesh N

    RSC advances

    2024  Volume 14, Issue 19, Page(s) 13336–13341

    Abstract: Chemically modified antisense oligonucleotide (ASO) has been established as a successful therapeutic strategy for treating various human diseases. To date, ten ASO drugs, which are capable of either inducing mRNA ... ...

    Abstract Chemically modified antisense oligonucleotide (ASO) has been established as a successful therapeutic strategy for treating various human diseases. To date, ten ASO drugs, which are capable of either inducing mRNA degradation
    Language English
    Publishing date 2024-04-24
    Publishing country England
    Document type Journal Article
    ISSN 2046-2069
    ISSN (online) 2046-2069
    DOI 10.1039/d4ra01925c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evaluation of Chemically Modified Nucleic Acid Analogues for Splice Switching Application.

    Le, Bao T / Chen, Suxiang / Veedu, Rakesh N

    ACS omega

    2023  Volume 8, Issue 51, Page(s) 48650–48661

    Abstract: In recent years, several splice switching antisense oligonucleotide (ASO)-based therapeutics have gained significant interest, and several candidates received approval for clinical use for treating rare diseases, in particular, Duchenne muscular ... ...

    Abstract In recent years, several splice switching antisense oligonucleotide (ASO)-based therapeutics have gained significant interest, and several candidates received approval for clinical use for treating rare diseases, in particular, Duchenne muscular dystrophy and spinal muscular atrophy. These ASOs are fully modified; in other words, they are composed of chemically modified nucleic acid analogues instead of natural RNA oligomers. This has significantly improved drug-like properties of these ASOs in terms of efficacy, stability, pharmacokinetics, and safety. Although chemical modifications of oligonucleotides have been discussed previously for numerous applications including nucleic acid aptamers, small interfering RNA, DNAzyme, and ASO, to the best of our knowledge, none of them have solely focused on the analogues that have been utilized for splice switching applications. To this end, we present here a comprehensive review of different modified nucleic acid analogues that have been explored for developing splice switching ASOs. In addition to the antisense chemistry, we also endeavor to provide a brief historical overview of the approved spice switching ASO drugs, including a list of drugs that have entered human clinical trials. We hope this work will inspire further investigations into expanding the potential of novel nucleic acid analogues for constructing splice switching ASOs.
    Language English
    Publishing date 2023-12-11
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2470-1343
    ISSN (online) 2470-1343
    DOI 10.1021/acsomega.3c07618
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Aptamer-engineered (nano)materials for theranostic applications.

    Rabiee, Navid / Chen, Suxiang / Ahmadi, Sepideh / Veedu, Rakesh N

    Theranostics

    2023  Volume 13, Issue 15, Page(s) 5183–5206

    Abstract: A diverse array of organic and inorganic materials, including nanomaterials, has been extensively employed in multifunctional biomedical applications. These applications encompass drug/gene delivery, tissue engineering, biosensors, photodynamic and ... ...

    Abstract A diverse array of organic and inorganic materials, including nanomaterials, has been extensively employed in multifunctional biomedical applications. These applications encompass drug/gene delivery, tissue engineering, biosensors, photodynamic and photothermal therapy, and combinatorial sciences. Surface and bulk engineering of these materials, by incorporating biomolecules and aptamers, offers several advantages such as decreased cytotoxicity, improved stability, enhanced selectivity/sensitivity toward specific targets, and expanded multifunctional capabilities. In this comprehensive review, we specifically focus on aptamer-modified engineered materials for diverse biomedical applications. We delve into their mechanisms, advantages, and challenges, and provide an in-depth analysis of relevant literature references. This critical evaluation aims to enhance the scientific community's understanding of this field and inspire new ideas for future research endeavors.
    MeSH term(s) Precision Medicine ; Drug Delivery Systems ; Nanostructures/therapeutic use ; Aptamers, Nucleotide ; Biosensing Techniques
    Chemical Substances Aptamers, Nucleotide
    Language English
    Publishing date 2023-09-25
    Publishing country Australia
    Document type Journal Article ; Review
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.85419
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Splice-Switching Antisense Oligonucleotides Targeting Extra- and Intracellular Domains of Epidermal Growth Factor Receptor in Cancer Cells.

    Balachandran, Akilandeswari Ashwini / Raguraman, Prithi / Rahimizadeh, Kamal / Veedu, Rakesh N

    Biomedicines

    2023  Volume 11, Issue 12

    Abstract: Cancer is one of the leading causes of death globally. Epidermal growth factor receptor is one of the proteins involved in cancer cell proliferation, differentiation, and invasion. Antisense oligonucleotides are chemical nucleic acids that bind to target ...

    Abstract Cancer is one of the leading causes of death globally. Epidermal growth factor receptor is one of the proteins involved in cancer cell proliferation, differentiation, and invasion. Antisense oligonucleotides are chemical nucleic acids that bind to target messenger ribonucleic acid and modulate its expression. Herein, we demonstrate the efficacy of splice-modulating antisense oligonucleotides to target specific exons in the extracellular (exon 3) and intracellular (exon 18, 21) domains of epidermal growth factor receptor. These antisense oligonucleotides were synthesized as 25mer 2'-O methyl phosphorothioate-modified ribonucleic acids that bind to complementary specific regions in respective exons. We found that PNAT524, PNAT525, PNAT576, and PNAT578 effectively skipped exon 3, exon 18, and exon 21 in glioblastoma, liver cancer, and breast cancer cell lines. PNAT578 treatment also skipped partial exon 19, complete exon 20, and partial exon 21 in addition to complete exon 21 skipping. We also found that a cocktail of PNAT576 and PNAT578 antisense oligonucleotides performed better than their individual counterparts. The migration potential of glioblastoma cancer cells was reduced to a greater extent after treatment with these antisense oligonucleotides. We firmly believe that using these splice-modulating antisense oligonucleotides in combination with existing EGFR-targeted therapies could improve therapeutic outcomes.
    Language English
    Publishing date 2023-12-13
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11123299
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Phosphorothioate modification improves exon-skipping of antisense oligonucleotides based on sulfonyl phosphoramidates in

    Su, Yongdong / Raguraman, Prithi / Veedu, Rakesh N / Filichev, Vyacheslav V

    Organic & biomolecular chemistry

    2022  Volume 20, Issue 18, Page(s) 3790–3797

    Abstract: 2'- ...

    Abstract 2'-
    MeSH term(s) Amides ; Animals ; Exons/genetics ; Mice ; Mice, Inbred mdx ; Muscle Fibers, Skeletal ; Oligonucleotides, Antisense/genetics ; Phosphates ; Phosphoric Acids ; Phosphorothioate Oligonucleotides ; RNA
    Chemical Substances Amides ; Oligonucleotides, Antisense ; Phosphates ; Phosphoric Acids ; Phosphorothioate Oligonucleotides ; RNA (63231-63-0) ; phosphoramidic acid (9Q189608GB)
    Language English
    Publishing date 2022-05-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2097583-1
    ISSN 1477-0539 ; 1477-0520
    ISSN (online) 1477-0539
    ISSN 1477-0520
    DOI 10.1039/d2ob00304j
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Splice-Switching Antisense Oligonucleotides Targeting Extra- and Intracellular Domains of Epidermal Growth Factor Receptor in Cancer Cells

    Akilandeswari Ashwini Balachandran / Prithi Raguraman / Kamal Rahimizadeh / Rakesh N. Veedu

    Biomedicines, Vol 11, Iss 12, p

    2023  Volume 3299

    Abstract: Cancer is one of the leading causes of death globally. Epidermal growth factor receptor is one of the proteins involved in cancer cell proliferation, differentiation, and invasion. Antisense oligonucleotides are chemical nucleic acids that bind to target ...

    Abstract Cancer is one of the leading causes of death globally. Epidermal growth factor receptor is one of the proteins involved in cancer cell proliferation, differentiation, and invasion. Antisense oligonucleotides are chemical nucleic acids that bind to target messenger ribonucleic acid and modulate its expression. Herein, we demonstrate the efficacy of splice-modulating antisense oligonucleotides to target specific exons in the extracellular (exon 3) and intracellular (exon 18, 21) domains of epidermal growth factor receptor. These antisense oligonucleotides were synthesized as 25mer 2′-O methyl phosphorothioate-modified ribonucleic acids that bind to complementary specific regions in respective exons. We found that PNAT524, PNAT525, PNAT576, and PNAT578 effectively skipped exon 3, exon 18, and exon 21 in glioblastoma, liver cancer, and breast cancer cell lines. PNAT578 treatment also skipped partial exon 19, complete exon 20, and partial exon 21 in addition to complete exon 21 skipping. We also found that a cocktail of PNAT576 and PNAT578 antisense oligonucleotides performed better than their individual counterparts. The migration potential of glioblastoma cancer cells was reduced to a greater extent after treatment with these antisense oligonucleotides. We firmly believe that using these splice-modulating antisense oligonucleotides in combination with existing EGFR-targeted therapies could improve therapeutic outcomes.
    Keywords epidermal growth factor receptor ; splice-switching antisense oligonucleotides ; glioblastoma ; liver cancer ; breast cancer ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Novel 3'-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3'-deoxythymidine analogues: Design, synthesis, characterization and their potential as anticancer agents.

    Ankit / Kumar, Ritik / Wang, Tao / Veedu, Rakesh N / Kumar, Surender

    Nucleosides, nucleotides & nucleic acids

    2022  Volume 41, Issue 4, Page(s) 343–360

    Abstract: Novel 3'-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3'-deoxythymidine analogues ( ...

    Abstract Novel 3'-[4-fluoroaryl-(1,2,3-triazol-1-yl)]-3'-deoxythymidine analogues (
    MeSH term(s) Antineoplastic Agents/chemistry ; Cell Line, Tumor ; Glioblastoma/drug therapy ; Humans ; Structure-Activity Relationship ; Thymidine/analogs & derivatives ; Thymidine/chemistry ; Triazoles/chemistry
    Chemical Substances Antineoplastic Agents ; Triazoles ; Thymidine (VC2W18DGKR)
    Language English
    Publishing date 2022-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2008956-9
    ISSN 1532-2335 ; 1525-7770
    ISSN (online) 1532-2335
    ISSN 1525-7770
    DOI 10.1080/15257770.2022.2029883
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3870: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.

    Chen, Suxiang / Heendeniya, Saumya Nishanga / Le, Bao T / Rahimizadeh, Kamal / Rabiee, Navid / Zahra, Qurat Ul Ain / Veedu, Rakesh N

    BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy

    2024  Volume 38, Issue 2, Page(s) 177–203

    Abstract: ... N-of-1" study of milasen, an investigational ASO drug for Batten disease. Although for IEM, owing ...

    Abstract The last decade (2013-2023) has seen unprecedented successes in the clinical translation of therapeutic antisense oligonucleotides (ASOs). Eight such molecules have been granted marketing approval by the United States Food and Drug Administration (US FDA) during the decade, after the first ASO drug, fomivirsen, was approved much earlier, in 1998. Splice-modulating ASOs have also been developed for the therapy of inborn errors of metabolism (IEMs), due to their ability to redirect aberrant splicing caused by mutations, thus recovering the expression of normal transcripts, and correcting the deficiency of functional proteins. The feasibility of treating IEM patients with splice-switching ASOs has been supported by FDA permission (2018) of the first "N-of-1" study of milasen, an investigational ASO drug for Batten disease. Although for IEM, owing to the rarity of individual disease and/or pathogenic mutation, only a low number of patients may be treated by ASOs that specifically suppress the aberrant splicing pattern of mutant precursor mRNA (pre-mRNA), splice-switching ASOs represent superior individualized molecular therapeutics for IEM. In this work, we first summarize the ASO technology with respect to its mechanisms of action, chemical modifications of nucleotides, and rational design of modified oligonucleotides; following that, we precisely provide a review of the current understanding of developing splice-modulating ASO-based therapeutics for IEM. In the concluding section, we suggest potential ways to improve and/or optimize the development of ASOs targeting IEM.
    MeSH term(s) Humans ; Metabolic Diseases/drug therapy ; Metabolic Diseases/genetics ; Oligonucleotides, Antisense/therapeutic use ; United States
    Chemical Substances Oligonucleotides, Antisense
    Language English
    Publishing date 2024-01-22
    Publishing country New Zealand
    Document type Review ; Journal Article
    ZDB-ID 1364202-9
    ISSN 1179-190X ; 1173-8804
    ISSN (online) 1179-190X
    ISSN 1173-8804
    DOI 10.1007/s40259-024-00644-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4112: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: Evaluation of DNA segments in 2'-modified RNA sequences in designing efficient splice switching antisense oligonucleotides.

    Le, Bao T / Agarwal, Sudhir / Veedu, Rakesh N

    RSC advances

    2021  Volume 11, Issue 23, Page(s) 14029–14035

    Abstract: Synthetic antisense oligonucleotides (ASOs) have emerged as one of the most promising therapeutic approaches. So far, nine ASO drugs have received approval for clinical use, and four of them are based on splice-switching principles demonstrating the ... ...

    Abstract Synthetic antisense oligonucleotides (ASOs) have emerged as one of the most promising therapeutic approaches. So far, nine ASO drugs have received approval for clinical use, and four of them are based on splice-switching principles demonstrating the impact of ASO-mediated splice modulation. Notably, three among them (Exondys 51, Vyondys 53 and Viltepso) are based on phosphorodiamidate morpholino (PMO) chemistry whereas Spinraza is based on 2'-
    Language English
    Publishing date 2021-04-13
    Publishing country England
    Document type Journal Article
    ISSN 2046-2069
    ISSN (online) 2046-2069
    DOI 10.1039/d1ra00878a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: DNAzymes: Expanding the Potential of Nucleic Acid Therapeutics.

    Larcher, Leon M / Pitout, Ianthe L / Keegan, Niall P / Veedu, Rakesh N / Fletcher, Sue

    Nucleic acid therapeutics

    2023  Volume 33, Issue 3, Page(s) 178–192

    Abstract: Nucleic acids drugs have been proven in the clinic as a powerful modality to treat inherited and acquired diseases. However, key challenges including drug stability, renal clearance, cellular uptake, and movement across biological barriers (foremost the ... ...

    Abstract Nucleic acids drugs have been proven in the clinic as a powerful modality to treat inherited and acquired diseases. However, key challenges including drug stability, renal clearance, cellular uptake, and movement across biological barriers (foremost the blood-brain barrier) limit the translation and clinical efficacy of nucleic acid-based therapies, both systemically and in the central nervous system. In this study we provide an overview of an emerging class of nucleic acid therapeutic, called DNAzymes. In particular, we review the use of chemical modifications and carrier molecules for the stabilization and/or delivery of DNAzymes in cell and animal models. Although this review focuses on DNAzymes, the strategies described are broadly applicable to most nucleic acid technologies. This review should serve as a general guide for selecting chemical modifications to improve the therapeutic performance of DNAzymes.
    MeSH term(s) Animals ; DNA, Catalytic/genetics ; DNA, Catalytic/therapeutic use ; DNA, Catalytic/chemistry ; RNA/chemistry
    Chemical Substances DNA, Catalytic ; RNA (63231-63-0)
    Language English
    Publishing date 2023-04-21
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2639888-6
    ISSN 2159-3345 ; 2159-3337
    ISSN (online) 2159-3345
    ISSN 2159-3337
    DOI 10.1089/nat.2022.0066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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