Building a chimera of aptamer–antisense oligonucleotide for silencing galectin-1 gene

Author(s): Shanni Hong ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Na Sun ⁵ ^, ⁶ ^, ⁷ ^, ⁴ , Min Liu ⁵ ^, ⁶ ^, ⁷ ^, ⁴ , Jine Wang ⁵ ^, ⁶ ^, ⁷ ^, ⁴ , Renjun Pei ⁵ ^, ⁶ ^, ⁷ ^, ⁴

Publication date (Electronic): 2016

Journal: RSC Advances

Publisher: Royal Society of Chemistry (RSC)

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Abstract

Galectin-1 is closely related with immune systems, and its overexpression may cause tumor metastasis.

Abstract

Galectin-1 is closely related with immune systems, and its overexpression may cause tumor metastasis. Owing to the better stability of antisense oligonucleotides than siRNA, we constructed a chimera of aptamer–antisense oligonucleotide (Apt–AS) for silencing the galectin-1 gene specifically. For studying the endocytosis pathways of Apt–AS by aptamer targeted delivery, we marked the 3′ terminus of Apt–AS with Alexa Flour 488 (Apt–AS488) so as to trace the pathways through the confocal microscope. Furthermore, Apt–AS was used to silence the expression of galectin-1. The results showed Apt–AS entered cells by a caveolae mediated endocytosis pathway, and the aptamer–antisense chimeras did not impair the antisense gene silencing efficiency. Moreover Apt–AS could improve the cellular uptake and selectively entered cells.

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Galectin-1: a small protein with major functions.

Robert Kiss, Florence Lefranc, Marie Le Mercier … (2006)

Galectins are a family of carbohydrate-binding proteins with an affinity for beta-galactosides. Galectin-1 (Gal-1) is differentially expressed by various normal and pathological tissues and appears to be functionally polyvalent, with a wide range of biological activity. The intracellular and extracellular activity of Gal-1 has been described. Evidence points to Gal-1 and its ligands as one of the master regulators of such immune responses as T-cell homeostasis and survival, T-cell immune disorders, inflammation and allergies as well as host-pathogen interactions. Gal-1 expression or overexpression in tumors and/or the tissue surrounding them must be considered as a sign of the malignant tumor progression that is often related to the long-range dissemination of tumoral cells (metastasis), to their dissemination into the surrounding normal tissue, and to tumor immune-escape. Gal-1 in its oxidized form plays a number of important roles in the regeneration of the central nervous system after injury. The targeted overexpression (or delivery) of Gal-1 should be considered as a method of choice for the treatment of some kinds of inflammation-related diseases, neurodegenerative pathologies and muscular dystrophies. In contrast, the targeted inhibition of Gal-1 expression is what should be developed for therapeutic applications against cancer progression. Gal-1 is thus a promising molecular target for the development of new and original therapeutic tools.

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Aptamer-integrated DNA nanostructures for biosensing, bioimaging and cancer therapy.

Hong-Min Meng, Hui Liu, Hailan Kuai … (2016)

The combination of nanostructures with biomolecules leading to the generation of functional nanosystems holds great promise for biotechnological and biomedical applications. As a naturally occurring biomacromolecule, DNA exhibits excellent biocompatibility and programmability. Also, scalable synthesis can be readily realized through automated instruments. Such unique properties, together with Watson-Crick base-pairing interactions, make DNA a particularly promising candidate to be used as a building block material for a wide variety of nanostructures. In the past few decades, various DNA nanostructures have been developed, including one-, two- and three-dimensional nanomaterials. Aptamers are single-stranded DNA or RNA molecules selected by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), with specific recognition abilities to their targets. Therefore, integrating aptamers into DNA nanostructures results in powerful tools for biosensing and bioimaging applications. Furthermore, owing to their high loading capability, aptamer-modified DNA nanostructures have also been altered to play the role of drug nanocarriers for in vivo applications and targeted cancer therapy. In this review, we summarize recent progress in the design of aptamers and related DNA molecule-integrated DNA nanostructures as well as their applications in biosensing, bioimaging and cancer therapy. To begin with, we first introduce the SELEX technology. Subsequently, the methodologies for the preparation of aptamer-integrated DNA nanostructures are presented. Then, we highlight their applications in biosensing and bioimaging for various targets, as well as targeted cancer therapy applications. Finally, we discuss several challenges and further opportunities in this emerging field.