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![Access through your institution Buy or subscribe Oligonucleotide is a short, versatile polynucleotide DNA or RNA chain that usually consists of 8–50 nucleotides. It could be an anti-sense oligonucleotide (ASO), a complementary chain of target mRNA, blocking the transcription process to proteins. It could act as an aptamer with strong affinity towards certain molecules. Besides, oligonucleotide could also be other functional molecules such as splice-switching oligonucleotide, anti-gene oligonucleotide, small interference RNA (siRNA), ribozymes, etc. Oligonucleotide possesses a general structure composed of ribose/deoxyribose, five types of bases (AGTCU) and phosphoric acid and thus it can be readily prepared by organic synthesis. In addition, oligonucleotides are believed to demonstrate higher specificity, lower side effect, less cytotoxicity and lower possibility to cause drug resistance than small molecule drugs. For these reasons, gene therapy using oligonucleotides has aroused great interest and tremendous efforts have been devoted to the use of oligonucleotide therapies for the treatment of various diseases in the past decades. In 1978, Zamecnik and Stephenson firstly demonstrated a synthetic ASO with 13 nucleotides that can effectively inhibit the virus replication [1]. Later since Vitravene (Fomivirsen), an ASO, was firstly approved by FDA in 1998 for the treatment of patients with peripheral cytomegalovirus (CMV) retinitis complicated with AIDS [2], during the past 20 years, several oligonucleotide therapies have then been subsequently approved for the treatment of other diseases [3]. However, some technical challenges still need to be addressed to accelerate the development of oligonucleotide therapies. The first issue is related to the fragility and instability of the oligonucleotide, especially the single-strand oligonucleotide, which can be easily degraded by intracellular nuclease [4]. And it is noted that approximately half of the oligonucleotide drugs approved by FDA nowadays are single-strand oligonucleotides. The second issue is that oligonucleotides need to be precisely delivered to the target tissue and the right intracellular compartment before it could take effect [5], but naked or unmodified oligonucleotides are usually negatively charged and are poorly internalized by cells [6]. At last, oligonucleotide therapies usually have dose requirement, and dose below the threshold would result in inefficient therapies [7]. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 6 print issues and online access $259.00 per year only $43.17 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Bonn D. Prospects for antisense therapy are looking brighter. Lancet. 1996;347:820. Article CAS Google Scholar * The Vitravene Study Group. A randomized controlled clinical trial of intravitreous Fomivirsen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with aids. Am J Ophthalmol. 2002;133:467–74. Article Google Scholar * Stein CA, Castanotto D. FDA-approved oligonucleotide therapies in 2017. Mol Ther. 2017;25:1069–75. Article CAS Google Scholar * Sun Y, Zhao Y, Zhao X, Lee RJ, Teng L, Zhou C. Enhancing the therapeutic delivery of oligonucleotides by chemical modification and nanoparticle encapsulation. Molecules. 2017;22:E1724. Article Google Scholar * Juliano RL. The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 2016;44:6518–48. Article Google Scholar * Kole R, Krainer AR, Altman S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat Rev Drug Discov. 2012;11:125–40. Article CAS Google Scholar * Khvorova A, Watts JK. The chemical evolution of oligonucleotide therapies of clinical utility. Nat Biotechnol. 2017;35:238–48. Article CAS Google Scholar * Geary RS, Henry SP, Grillone LR. Fomivirsen: clinical pharmacology and potential drug interactions. Clin Pharmacokinet. 2002;41:255–60. Article CAS Google Scholar * Liu H, Wang H, Yang W, Cheng Y. Disulfide cross-linked low generation dendrimers with high gene transfection efficacy, low cytotoxicity, and low cost. J Am Chem Soc. 2012;134:17680–7. Article CAS Google Scholar * Shen W, Wang Q, Shen Y, Gao X, Li L, Yan Y, et al. Green tea catechin dramatically promotes RNAi mediated by low-molecular-weight polymers. ACS Cent Sci. 2018;4:1326–33. Article CAS Google Scholar * Shen W, Wang R, Fan Q, Gao X, Wang H, Shen Y, et al. Natural polyphenol inspired polycatechols for efficient siRNA delivery. CCS Chem. 2020;2:146–57. Article CAS Google Scholar * Shen Y, Zhu F, Shen W, Fan Q, Li Y, Cheng Y. Structure-function relationship of plant polyphenols for promoted siRNA delivery. Chem J Chin Univ. 2020;41:633–8. Google Scholar * Shen W, Wang R, Fan Q, Li Y, Cheng Y. Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers. Gene Ther. https://doi.org/10.1038/s41434-020-0151-y. * Chung JE, Tan S, Gao SJ, Yongvongsoontorn N, Kim SH, Lee JH, et al. Self-assembled micellar nanocomplexes comprising green tea catechin derivatives and protein drugs for cancer therapy. Nat Nanotechnol. 2014;9:907–12. Article CAS Google Scholar Download references FUNDING This work was supported by the Beijing Natural Science Foundation (JQ18006). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Key Laboratory of Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Tsinghua University, 100084, Beijing, China Yuanyu Zhang & Jun Ge Authors * Yuanyu Zhang View author publications You can also search for this author inPubMed Google Scholar * Jun Ge View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jun Ge. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Zhang, Y., Ge, J. Green nanoparticles for oligonucleotide delivery. _Gene Ther_ 27, 535–536 (2020). https://doi.org/10.1038/s41434-020-0173-5 Download citation * Received: 07 May 2020 * Revised: 16 June 2020 * Accepted: 01 July 2020 * Published: 10 July 2020 * Issue Date: December 2020 * DOI: https://doi.org/10.1038/s41434-020-0173-5 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. 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Access through your institution Buy or subscribe Oligonucleotide is a short, versatile polynucleotide DNA or RNA chain that usually consists of 8–50 nucleotides. It could be an anti-sense
oligonucleotide (ASO), a complementary chain of target mRNA, blocking the transcription process to proteins. It could act as an aptamer with strong affinity towards certain molecules.
Besides, oligonucleotide could also be other functional molecules such as splice-switching oligonucleotide, anti-gene oligonucleotide, small interference RNA (siRNA), ribozymes, etc.
Oligonucleotide possesses a general structure composed of ribose/deoxyribose, five types of bases (AGTCU) and phosphoric acid and thus it can be readily prepared by organic synthesis. In
addition, oligonucleotides are believed to demonstrate higher specificity, lower side effect, less cytotoxicity and lower possibility to cause drug resistance than small molecule drugs. For
these reasons, gene therapy using oligonucleotides has aroused great interest and tremendous efforts have been devoted to the use of oligonucleotide therapies for the treatment of various
diseases in the past decades. In 1978, Zamecnik and Stephenson firstly demonstrated a synthetic ASO with 13 nucleotides that can effectively inhibit the virus replication [1]. Later since
Vitravene (Fomivirsen), an ASO, was firstly approved by FDA in 1998 for the treatment of patients with peripheral cytomegalovirus (CMV) retinitis complicated with AIDS [2], during the past
20 years, several oligonucleotide therapies have then been subsequently approved for the treatment of other diseases [3]. However, some technical challenges still need to be addressed to
accelerate the development of oligonucleotide therapies. The first issue is related to the fragility and instability of the oligonucleotide, especially the single-strand oligonucleotide,
which can be easily degraded by intracellular nuclease [4]. And it is noted that approximately half of the oligonucleotide drugs approved by FDA nowadays are single-strand oligonucleotides.
The second issue is that oligonucleotides need to be precisely delivered to the target tissue and the right intracellular compartment before it could take effect [5], but naked or unmodified
oligonucleotides are usually negatively charged and are poorly internalized by cells [6]. At last, oligonucleotide therapies usually have dose requirement, and dose below the threshold
would result in inefficient therapies [7]. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal
Receive 6 print issues and online access $259.00 per year only $43.17 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may
be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support
REFERENCES * Bonn D. Prospects for antisense therapy are looking brighter. Lancet. 1996;347:820. Article CAS Google Scholar * The Vitravene Study Group. A randomized controlled clinical
trial of intravitreous Fomivirsen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with aids. Am J Ophthalmol. 2002;133:467–74. Article Google Scholar *
Stein CA, Castanotto D. FDA-approved oligonucleotide therapies in 2017. Mol Ther. 2017;25:1069–75. Article CAS Google Scholar * Sun Y, Zhao Y, Zhao X, Lee RJ, Teng L, Zhou C. Enhancing
the therapeutic delivery of oligonucleotides by chemical modification and nanoparticle encapsulation. Molecules. 2017;22:E1724. Article Google Scholar * Juliano RL. The delivery of
therapeutic oligonucleotides. Nucleic Acids Res. 2016;44:6518–48. Article Google Scholar * Kole R, Krainer AR, Altman S. RNA therapeutics: beyond RNA interference and antisense
oligonucleotides. Nat Rev Drug Discov. 2012;11:125–40. Article CAS Google Scholar * Khvorova A, Watts JK. The chemical evolution of oligonucleotide therapies of clinical utility. Nat
Biotechnol. 2017;35:238–48. Article CAS Google Scholar * Geary RS, Henry SP, Grillone LR. Fomivirsen: clinical pharmacology and potential drug interactions. Clin Pharmacokinet.
2002;41:255–60. Article CAS Google Scholar * Liu H, Wang H, Yang W, Cheng Y. Disulfide cross-linked low generation dendrimers with high gene transfection efficacy, low cytotoxicity, and
low cost. J Am Chem Soc. 2012;134:17680–7. Article CAS Google Scholar * Shen W, Wang Q, Shen Y, Gao X, Li L, Yan Y, et al. Green tea catechin dramatically promotes RNAi mediated by
low-molecular-weight polymers. ACS Cent Sci. 2018;4:1326–33. Article CAS Google Scholar * Shen W, Wang R, Fan Q, Gao X, Wang H, Shen Y, et al. Natural polyphenol inspired polycatechols
for efficient siRNA delivery. CCS Chem. 2020;2:146–57. Article CAS Google Scholar * Shen Y, Zhu F, Shen W, Fan Q, Li Y, Cheng Y. Structure-function relationship of plant polyphenols for
promoted siRNA delivery. Chem J Chin Univ. 2020;41:633–8. Google Scholar * Shen W, Wang R, Fan Q, Li Y, Cheng Y. Natural polyphenol assisted delivery of single-strand oligonucleotides by
cationic polymers. Gene Ther. https://doi.org/10.1038/s41434-020-0151-y. * Chung JE, Tan S, Gao SJ, Yongvongsoontorn N, Kim SH, Lee JH, et al. Self-assembled micellar nanocomplexes
comprising green tea catechin derivatives and protein drugs for cancer therapy. Nat Nanotechnol. 2014;9:907–12. Article CAS Google Scholar Download references FUNDING This work was
supported by the Beijing Natural Science Foundation (JQ18006). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Key Laboratory of Industrial Biocatalysis, Ministry of Education, Department of
Chemical Engineering, Tsinghua University, 100084, Beijing, China Yuanyu Zhang & Jun Ge Authors * Yuanyu Zhang View author publications You can also search for this author inPubMed
Google Scholar * Jun Ge View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jun Ge. ETHICS DECLARATIONS CONFLICT OF
INTEREST The authors declare that they have no conflict of interest. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published
maps and institutional affiliations. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Zhang, Y., Ge, J. Green nanoparticles for oligonucleotide delivery.
_Gene Ther_ 27, 535–536 (2020). https://doi.org/10.1038/s41434-020-0173-5 Download citation * Received: 07 May 2020 * Revised: 16 June 2020 * Accepted: 01 July 2020 * Published: 10 July
2020 * Issue Date: December 2020 * DOI: https://doi.org/10.1038/s41434-020-0173-5 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable
link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative