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The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions

Hematologic malignancies, including leukemia, lymphoma, myeloproliferative disorder and plasma cell neoplasia, are genetically heterogeneous and characterized by an uncontrolled proliferation of their corresponding cell lineages in the bone marrow, peripheral blood, tissues or plasma. Although there...

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Autores principales: Wang, Si Chun, Yan, Xing Yi, Yang, Chang, Naranmandura, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687288/
https://www.ncbi.nlm.nih.gov/pubmed/36354547
http://dx.doi.org/10.3390/bioengineering9110635
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author Wang, Si Chun
Yan, Xing Yi
Yang, Chang
Naranmandura, Hua
author_facet Wang, Si Chun
Yan, Xing Yi
Yang, Chang
Naranmandura, Hua
author_sort Wang, Si Chun
collection PubMed
description Hematologic malignancies, including leukemia, lymphoma, myeloproliferative disorder and plasma cell neoplasia, are genetically heterogeneous and characterized by an uncontrolled proliferation of their corresponding cell lineages in the bone marrow, peripheral blood, tissues or plasma. Although there are many types of therapeutic drugs (e.g., TKIs, chemotherapy drugs) available for treatment of different malignancies, the relapse, drug resistance and severe side effects due to the lack of selectivity seriously limit their clinical application. Currently, although antibody–drug conjugates have been well established as able to target and deliver highly potent chemotherapy agents into cancer cells for the reduction of damage to healthy cells and have achieved success in leukemia treatment, they still also have shortcomings such as high cost, high immunogenicity and low stability. Aptamers are ssDNA or RNA oligonucleotides that can also precisely deliver therapeutic agents into cancer cells through specifically recognizing the membrane protein on cancer cells, which is similar to the capabilities of monoclonal antibodies. Aptamers exhibit higher binding affinity, lower immunogenicity and higher thermal stability than antibodies. Therefore, in this review we comprehensively describe recent advances in the development of aptamer–drug conjugates (ApDCs) with cytotoxic payload through chemical linkers or direct incorporation, as well as further introduce the latest promising aptamers-based therapeutic strategies such as aptamer–T cell therapy and aptamer–PROTAC, clarifying their bright application, development direction and challenges in the treatment of hematologic malignancies.
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spelling pubmed-96872882022-11-25 The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions Wang, Si Chun Yan, Xing Yi Yang, Chang Naranmandura, Hua Bioengineering (Basel) Review Hematologic malignancies, including leukemia, lymphoma, myeloproliferative disorder and plasma cell neoplasia, are genetically heterogeneous and characterized by an uncontrolled proliferation of their corresponding cell lineages in the bone marrow, peripheral blood, tissues or plasma. Although there are many types of therapeutic drugs (e.g., TKIs, chemotherapy drugs) available for treatment of different malignancies, the relapse, drug resistance and severe side effects due to the lack of selectivity seriously limit their clinical application. Currently, although antibody–drug conjugates have been well established as able to target and deliver highly potent chemotherapy agents into cancer cells for the reduction of damage to healthy cells and have achieved success in leukemia treatment, they still also have shortcomings such as high cost, high immunogenicity and low stability. Aptamers are ssDNA or RNA oligonucleotides that can also precisely deliver therapeutic agents into cancer cells through specifically recognizing the membrane protein on cancer cells, which is similar to the capabilities of monoclonal antibodies. Aptamers exhibit higher binding affinity, lower immunogenicity and higher thermal stability than antibodies. Therefore, in this review we comprehensively describe recent advances in the development of aptamer–drug conjugates (ApDCs) with cytotoxic payload through chemical linkers or direct incorporation, as well as further introduce the latest promising aptamers-based therapeutic strategies such as aptamer–T cell therapy and aptamer–PROTAC, clarifying their bright application, development direction and challenges in the treatment of hematologic malignancies. MDPI 2022-11-02 /pmc/articles/PMC9687288/ /pubmed/36354547 http://dx.doi.org/10.3390/bioengineering9110635 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wang, Si Chun
Yan, Xing Yi
Yang, Chang
Naranmandura, Hua
The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions
title The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions
title_full The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions
title_fullStr The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions
title_full_unstemmed The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions
title_short The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions
title_sort landscape of nucleic-acid-based aptamers for treatment of hematologic malignancies: challenges and future directions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687288/
https://www.ncbi.nlm.nih.gov/pubmed/36354547
http://dx.doi.org/10.3390/bioengineering9110635
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