Green nanoparticles for oligonucleotide delivery

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 RELEVANT ARTICLES Open Access articles citing this article. * NANOMATERIALS

IN CANCER IMMUNOTHERAPY: TARGETING CANCER-ASSOCIATED FIBROBLASTS * Zhongsong Zhang *  & Long Chen _Cancer Nanotechnology_ Open Access 17 January 2025 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