Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells
Oligonucleotide therapeutics, antisense oligonucleotides (ASOs) and short interfering RNA (siRNA) are short synthetic nucleic acid molecules with a promising potential to treat a wide range of diseases. Despite considerable progress in the field, the development of safe and effective delivery system...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/9/2096 |
| _version_ | 1797490914339323904 |
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| author | Mauro Sousa de Almeida Barbara Rothen-Rutishauser Michael Mayer Maria Taskova |
| author_facet | Mauro Sousa de Almeida Barbara Rothen-Rutishauser Michael Mayer Maria Taskova |
| author_sort | Mauro Sousa de Almeida |
| collection | DOAJ |
| description | Oligonucleotide therapeutics, antisense oligonucleotides (ASOs) and short interfering RNA (siRNA) are short synthetic nucleic acid molecules with a promising potential to treat a wide range of diseases. Despite considerable progress in the field, the development of safe and effective delivery systems that target organs and tissues other than the liver is challenging. While keeping possible off-target oligonucleotide interactions and toxicity related to chemical modifications in mind, innovative solutions for targeted intracellular delivery are highly needed. Herein, we report on the design, synthesis and testing of a novel multi-modified and multi-functionalized heteroduplex oligonucleotide (HDO) with respect to its intracellular delivery and its ability to silence genes in HeLa cells. Simultaneously, folic acid- and peptide- labeled HDO show proficient silencing of the green fluorescent protein (GFP) gene with an 84% reduction in the GFP fluorescence. In addition, the Bcl2 HDO achieved effective Bcl2 gene knockdown in the cells. The data show the proficiency of the multi-functionalization strategy and provide an example for advancing the design of safe and efficient forthcoming oligonucleotide therapeutics, such as HDO. |
| first_indexed | 2024-03-10T00:39:52Z |
| format | Article |
| id | doaj.art-02591dece2d54d0e94ad71077e644e47 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:39:52Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-02591dece2d54d0e94ad71077e644e472023-11-23T15:09:04ZengMDPI AGBiomedicines2227-90592022-08-01109209610.3390/biomedicines10092096Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa CellsMauro Sousa de Almeida0Barbara Rothen-Rutishauser1Michael Mayer2Maria Taskova3BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, SwitzerlandBioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, SwitzerlandBiophysics, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, SwitzerlandBiophysics, Adolphe Merkle Institute, University of Fribourg, Chemin des Verdiers 4, 1700 Fribourg, SwitzerlandOligonucleotide therapeutics, antisense oligonucleotides (ASOs) and short interfering RNA (siRNA) are short synthetic nucleic acid molecules with a promising potential to treat a wide range of diseases. Despite considerable progress in the field, the development of safe and effective delivery systems that target organs and tissues other than the liver is challenging. While keeping possible off-target oligonucleotide interactions and toxicity related to chemical modifications in mind, innovative solutions for targeted intracellular delivery are highly needed. Herein, we report on the design, synthesis and testing of a novel multi-modified and multi-functionalized heteroduplex oligonucleotide (HDO) with respect to its intracellular delivery and its ability to silence genes in HeLa cells. Simultaneously, folic acid- and peptide- labeled HDO show proficient silencing of the green fluorescent protein (GFP) gene with an 84% reduction in the GFP fluorescence. In addition, the Bcl2 HDO achieved effective Bcl2 gene knockdown in the cells. The data show the proficiency of the multi-functionalization strategy and provide an example for advancing the design of safe and efficient forthcoming oligonucleotide therapeutics, such as HDO.https://www.mdpi.com/2227-9059/10/9/2096oligonucleotide therapeuticsdeliverymodified oligonucleotidesmulti-functionalizationgene knockdown |
| spellingShingle | Mauro Sousa de Almeida Barbara Rothen-Rutishauser Michael Mayer Maria Taskova Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells Biomedicines oligonucleotide therapeutics delivery modified oligonucleotides multi-functionalization gene knockdown |
| title | Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells |
| title_full | Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells |
| title_fullStr | Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells |
| title_full_unstemmed | Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells |
| title_short | Multi-Functionalized Heteroduplex Antisense Oligonucleotides for Targeted Intracellular Delivery and Gene Silencing in HeLa Cells |
| title_sort | multi functionalized heteroduplex antisense oligonucleotides for targeted intracellular delivery and gene silencing in hela cells |
| topic | oligonucleotide therapeutics delivery modified oligonucleotides multi-functionalization gene knockdown |
| url | https://www.mdpi.com/2227-9059/10/9/2096 |
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