» Articles » PMID: 16855294

H1 RNA Polymerase III Promoter-driven Expression of an RNA Aptamer Leads to High-level Inhibition of Intracellular Protein Activity

Overview
Specialty Biochemistry
Date 2006 Jul 21
PMID 16855294
Citations 19
Authors
Affiliations
Soon will be listed here.
Abstract

Aptamers offer advantages over other oligonucleotide-based approaches that artificially interfere with target gene function due to their ability to bind protein products of these genes with high affinity and specificity. However, RNA aptamers are limited in their ability to target intracellular proteins since even nuclease-resistant aptamers do not efficiently enter the intracellular compartments. Moreover, attempts at expressing RNA aptamers within mammalian cells through vector-based approaches have been hampered by the presence of additional flanking sequences in expressed RNA aptamers, which may alter their functional conformation. In this report, we successfully expressed a 'pure' RNA aptamer specific for NF-kappaB p50 protein (A-p50) utilizing an adenoviral vector employing the H1 RNA polymerase III promoter. Binding of the expressed aptamer to its target and subsequent inhibition of NF-kappaB mediated intracellular events were demonstrated in human lung adenocarcinoma cells (A549), murine mammary carcinoma cells (4T1) as well as a human tumor xenograft model. This success highlights the promise of RNA aptamers to effectively target intracellular proteins for in vitro discovery and in vivo applications.

Citing Articles

Therapeutic Potential of Aptamer-Protein Interactions.

Shraim A, Abdel Majeed B, Al-Binni M, Hunaiti A ACS Pharmacol Transl Sci. 2022; 5(12):1211-1227.

PMID: 36524009 PMC: 9745894. DOI: 10.1021/acsptsci.2c00156.


Cancer immunomodulation using bispecific aptamers.

Thomas B, Porciani D, Burke D Mol Ther Nucleic Acids. 2022; 27:894-915.

PMID: 35141049 PMC: 8803965. DOI: 10.1016/j.omtn.2022.01.008.


Programmable Synthetic Protein Circuits for the Identification and Suppression of Hepatocellular Carcinoma.

Han X, Yang J, Zeng F, Weng J, Zhang Y, Peng Q Mol Ther Oncolytics. 2020; 17:70-82.

PMID: 32322664 PMC: 7160531. DOI: 10.1016/j.omto.2020.03.008.


Aptamers: A Review of Their Chemical Properties and Modifications for Therapeutic Application.

Adachi T, Nakamura Y Molecules. 2019; 24(23).

PMID: 31766318 PMC: 6930564. DOI: 10.3390/molecules24234229.


At the Intersection of Biomaterials and Gene Therapy: Progress in Non-viral Delivery of Nucleic Acids.

Uludag H, Ubeda A, Ansari A Front Bioeng Biotechnol. 2019; 7:131.

PMID: 31214586 PMC: 6558074. DOI: 10.3389/fbioe.2019.00131.


References
1.
Hermann T, Patel D . Adaptive recognition by nucleic acid aptamers. Science. 2000; 287(5454):820-5. DOI: 10.1126/science.287.5454.820. View

2.
Mi J, Zhang X, Giangrande P, McNamara 2nd J, Nimjee S, Sarraf-Yazdi S . Targeted inhibition of alphavbeta3 integrin with an RNA aptamer impairs endothelial cell growth and survival. Biochem Biophys Res Commun. 2005; 338(2):956-63. DOI: 10.1016/j.bbrc.2005.10.043. View

3.
Cheng Q, Lee H, Li Y, Parks T, Cheng G . Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-kappaB inhibition. Oncogene. 2000; 19(42):4936-40. DOI: 10.1038/sj.onc.1203861. View

4.
Grad J, Zeng X, Boise L . Regulation of Bcl-xL: a little bit of this and a little bit of STAT. Curr Opin Oncol. 2000; 12(6):543-9. DOI: 10.1097/00001622-200011000-00006. View

5.
Slebos R, Taylor J . A novel host cell reactivation assay to assess homologous recombination capacity in human cancer cell lines. Biochem Biophys Res Commun. 2001; 281(1):212-9. DOI: 10.1006/bbrc.2001.4335. View