NanoScript: A Novel Tool for Gene Regulation Based on Nanoparticles with Benefits and Drawbacks

Cansel Firat; Ayşenur Öztürk; İbrahim Dağcı; Yağmur Ünver; Kübra Solak

EN

NanoScript: A Novel Tool for Gene Regulation Based on Nanoparticles with Benefits and Drawbacks

Abstract

Transcription factors (TFs) are proteins that act as key regulators of gene expression by binding to specific DNA sequences to activate or repress gene expression by interacting with specific regulatory elements in the genome. TFs typically have multiple functional domains that contribute to their regulatory functions. These basically consist of three domains: the Nuclear Localization Signal (NLS) Domain, the DNA Binding Domain (DBD), and the Activation Domain (AD). Through the coordinated interaction of these domains, TFs can fine-tune gene expression in response to various internal and external signals within the cell. The ability to modulate gene expression is essential for controlling fundamental cellular processes, regulating development, and responding to environmental stimuli. A defect in the complex mechanism of TFs has been associated with an increasing number of human diseases. Therefore, TF-based gene regulation studies are considered a promising approach for many biological applications. In this context, researchers aimed to copy the structural and functional properties of TFs using a nanoparticle-based platform known as NanoScript. By mimicking the behavior of natural TFs, NanoScript is designed to enable precise gene regulation and cellular reprogramming and offer new possibilities for controlled and targeted manipulation of gene expression. The primary goal of NanoScript is to regulate gene expression at the transcriptional level in a non-viral manner. NanoScript can activate specific genes by interacting with endogenous DNA and initiating transcriptional activity, serving as an alternative synthetic structure to proteins for gene manipulation and cellular reprogramming. The platform has potential for a variety of applications in the fields of stem cell biology, cancer therapy, and cellular reprogramming thanks to its tunable components (nanoparticles and surface components) and the ability to effectively regulate gene expression. However, NanoScript also has some limitations, such as the possibility of interacting with off-target genes. In this study, current studies and techniques of a nanoparticle-based TF mimic called NanoScript in the field of gene regulation are discussed, and the advantages and challenges of this technique are discussed.

Keywords

Gene regulation , nanoparticles , NanoScript , transcription factor , stem cell

References

1.Singh VK, Saini A, Kalsan M, Kumar N, Chandra R. Describing the stem cell potency: The various methods of functional assessment and in silico diagnostics. Vol. 4, Frontiers in Cell and Developmental Biology. 2016.
2.Larijani B, Esfahani EN, Amini P, Nikbin B, Alimoghaddam K, Amiri S, et al. Stem cell therapy in treatment of different diseases. Acta Med Iran. 2012;50(2).
3.Tabar V, Studer L. Pluripotent stem cells in regenerative medicine: Challenges and recent progress. Vol. 15, Nature Reviews Genetics. 2014.
4.Patel S, Pongkulapa T, Yin PT, Pandian GN, Rathnam C, Bando T, et al. Integrating Epigenetic Modulators into NanoScript for Enhanced Chondrogenesis of Stem Cells. J Am Chem Soc. 2015 Apr 15;137(14):4598–601.
5.Dardir K, Rathnam C, Lee KB. Nanoscript: A versatile nanoparticle-based synthetic transcription factor for innovative gene manipulation. In: Methods in Molecular Biology. Humana Press Inc.; 2017. p. 239–49.
6.Portela A, Esteller M. Epigenetic modifications and human disease. Vol. 28, Nature Biotechnology. 2010.
7.Bilic J, Izpisua Belmonte JC. Concise review: Induced pluripotent stem cells versus embryonic stem cells: Close enough or yet too far apart? Vol. 30, Stem Cells. 2012.
8.Patel S, Yin PT, Sugiyama H, Lee KB. Inducing Stem Cell Myogenesis Using NanoScript. ACS Nano. 2015 Jul 28;9(7):6909–17.
9.Patel S, Chueng STD, Yin PT, Dardir K, Song Z, Pasquale N, et al. Induction of Stem-Cell-Derived Functional Neurons by NanoScript-Based Gene Repression. Angewandte Chemie - International Edition. 2015 Oct 1;54(41):11983–8.
10.Spitz F, Furlong EEM. Transcription factors: From enhancer binding to developmental control. Vol. 13, Nature Reviews Genetics. 2012.

11.Choi SO, Kim YC, Lee JW, Park JH, Prausnitz MR, Allen MG. Intracellular protein delivery and gene transfection by electroporation using a microneedle electrode array. Small. 2012;8(7).
12.Driscoll J, Yan IK, Patel T. Development of a Lyophilized Off-the-Shelf Mesenchymal Stem Cell-Derived Acellular Therapeutic. Pharmaceutics. 2022;14(4).
13.Tang R, Kim CS, Solfiell DJ, Rana S, Mout R, Velázquez-Delgado EM, et al. Direct delivery of functional proteins and enzymes to the cytosol using nanoparticle-stabilized nanocapsules. ACS Nano. 2013;7(8).
14.Elowitz MB, Leibier S. A synthetic oscillatory network of transcriptional regulators. Nature. 2000;403(6767).
15.Yazawa M, Sadaghiani AM, Hsueh B, Dolmetsch RE. Induction of protein-protein interactions in live cells using light. Nat Biotechnol. 2009;27(10).
16.Beerli RR, Dreier B, Barbas CF. Positive and negative regulation of endogenous genes by designed transcription factors. Proc Natl Acad Sci U S A. 2000;97(4).
17.Perez-Pinera P, Kocak DD, Vockley CM, Adler AF, Kabadi AM, Polstein LR, et al. RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods. 2013;10(10).
18.Schaming D, Remita H. Nanotechnology: from the ancient time to nowadays. Found Chem. 2015;17(3).
19.Buzea C, Pacheco II, Robbie K. Nanomaterials and nanoparticles: Sources and toxicity. Biointerphases. 2007;2(4):MR17–71.
20.Lines MG. Nanomaterials for practical functional uses. J Alloys Compd. 2008;449(1–2).
21.Barhoum A, García-Betancourt ML, Jeevanandam J, Hussien EA, Mekkawy SA, Mostafa M, et al. Review on Natural, Incidental, Bioinspired, and Engineered Nanomaterials: History, Definitions, Classifications, Synthesis, Properties, Market, Toxicities, Risks, and Regulations. Nanomaterials. 2022;12(2).
22.Bayda S, Adeel M, Tuccinardi T, Cordani M, Rizzolio F. The history of nanoscience and nanotechnology: From chemical-physical applications to nanomedicine. Vol. 25, Molecules. 2020.
23.Karn B, Kuiken T, Otto M. Nanotechnology and in situ remediation: A review of the benefits and potential risks. Vol. 117, Environmental Health Perspectives. 2009.
24.Nel A, Xia T, Mädler L, Li N. Toxic potential of materials at the nanolevel. Vol. 311, Science. 2006.
25.Morkoç H, Özgür Ü. Zinc Oxide: Fundamentals, Materials and Device Technology. Zinc Oxide: Fundamentals, Materials and Device Technology. 2009.
26.Wang Z, Liu H, Yang SH, Wang T, Liu C, Cao YC. Nanoparticle-based artificial RNA silencing machinery for antiviral therapy. Proc Natl Acad Sci U S A. 2012;109(31).
27.Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean AKR, Han MS, Mirkin CA. Oligonucleotide-Modified Gold Nanoparticles for Intracellular Gene Regulation. In: Spherical Nucleic Acids: Volume 4. 2021.
28.Patel S, Jung D, Yin PT, Carlton P, Yamamoto M, Bando T, et al. NanoScript: A nanoparticle-based artificial transcription factor for effective gene regulation. ACS Nano. 2014;8(9).
29.Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA. Gold nanoparticles for biology and medicine. Vol. 49, Angewandte Chemie - International Edition. 2010.
30.Gu Z, Biswas A, Zhao M, Tang Y. Tailoring nanocarriers for intracellular protein delivery. Chem Soc Rev. 2011;40(7).
31.Tang R, Kim CS, Solfiell DJ, Rana S, Mout R, Velázquez-Delgado EM, et al. Direct delivery of functional proteins and enzymes to the cytosol using nanoparticle-stabilized nanocapsules. ACS Nano. 2013;7(8).
32.Yan M, Du J, Gu Z, Liang M, Hu Y, Zhang W, et al. A novel intracellular protein delivery platform based on single-protein nanocapsules. Nat Nanotechnol. 2010;5(1).
33.Liu Y, Wang H, Kamei KI, Yan M, Chen KJ, Yuan Q, et al. Delivery of intact transcription factor by using self-assembled supramolecular nanoparticles. Angewandte Chemie - International Edition. 2011;50(13).
34.Leader B, Baca QJ, Golan DE. Protein therapeutics: A summary and pharmacological classification. Vol. 7, Nature Reviews Drug Discovery. 2008.
35.Xia Y, Pfeifer CR, Zhu K, Irianto J, Liu D, Pannell K, et al. Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle. Journal of Cell Biology. 2019;218(8).
36.Wente SR, Rout MP. The nuclear pore complex and nuclear transport. Vol. 2, Cold Spring Harbor perspectives in biology. 2010.
37.Patel S, Chueng STD, Yin PT, Dardir K, Song Z, Pasquale N, et al. Induction of Stem-Cell-Derived Functional Neurons by NanoScript-Based Gene Repression. Angewandte Chemie - International Edition. 2015;54(41).
38.Patel S, Pongkulapa T, Yin PT, Pandian GN, Rathnam C, Bando T, et al. Integrating Epigenetic Modulators into NanoScript for Enhanced Chondrogenesis of Stem Cells. J Am Chem Soc. 2015;137(14).
39.Pandian GN, Sugiyama H. Nature-inspired design of smart biomaterials using the chemical biology of nucleic acids. Bull Chem Soc Jpn. 2016;89(8).
40.Yang L, Rathnam C, Hidaka T, Hou Y, Conklin B, Pandian GN, et al. Nanoparticle-Based Artificial Mitochondrial DNA Transcription Regulator: MitoScript. Nano Lett. 2023;23(5).

Details

Primary Language

English

Subjects

Biochemistry and Cell Biology (Other)

Journal Section

Review Article

Authors

Cansel Firat ^*
0009-0007-5260-9095
Türkiye

Ayşenur Öztürk
0009-0005-6977-9483
Türkiye

İbrahim Dağcı
0000-0002-6354-2654
Türkiye

Yağmur Ünver
0000-0003-1497-081X
Türkiye

Kübra Solak
0000-0001-6643-3368
Türkiye

Publication Date

July 23, 2024

Submission Date

May 8, 2024

Acceptance Date

July 18, 2024

Published in Issue

Year 2024 Volume: 3 Number: 1

IZ

https://izlik.org/JA84XW63HS

APA

Firat, C., Öztürk, A., Dağcı, İ., Ünver, Y., & Solak, K. (2024). NanoScript: A Novel Tool for Gene Regulation Based on Nanoparticles with Benefits and Drawbacks. Eurasian Journal of Molecular and Biochemical Sciences, 3(1), 30-36. https://izlik.org/JA84XW63HS

NanoScript: A Novel Tool for Gene Regulation Based on Nanoparticles with Benefits and Drawbacks

Abstract

Keywords

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References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

IZ

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