A human epidermal growth factor receptor 3/heregulin interaction inhibitor aptamer discovered using SELEX

Yokoyama, Tetsuji; Ando, Tetsu; Iwamoto, Rina; Fuji, Daisuke; Kawakami, Takashi

doi:10.1016/j.bbrc.2021.03.076

Cited by 8 publications

(3 citation statements)

References 25 publications

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“…The identification of targeting aptamers can be achieved through SELEX, which enables screening of oligonucleotide libraries for aptamers with high binding affinity to specific cells or tissues. In recent years, the field has made significant progress in enhancing the specificity and selectivity of aptamer-siRNA conjugates through novel targeting strategies [ 138 ]. One such approach involves the use of multiple aptamers to target distinct receptors on the same cell or tissue, thereby reducing the risk of off-target effects and improving specificity.…”

Section: Strategies For Engineering Sirna Therapeuticsmentioning

confidence: 99%

“…One such approach involves the use of multiple aptamers to target distinct receptors on the same cell or tissue, thereby reducing the risk of off-target effects and improving specificity. An example is the aptamer-siRNA conjugate designed to target both EGFR and HER2 in breast cancer cells, which demonstrated enhanced selectivity and efficacy [ 138 , 139 ]. Another strategy entails targeting tumor-associated antigens (TAAs), proteins that are overexpressed on the surface of cancer cells but absent on normal cells, utilizing aptamers that target TAAs can significantly enhance the specificity of the conjugate and reduce off-target effects.…”

Section: Strategies For Engineering Sirna Therapeuticsmentioning

confidence: 99%

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Engineering siRNA therapeutics: challenges and strategies

Ali Zaidi,

Fatima,

Ali Zaidi

et al. 2023

J Nanobiotechnol

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Small interfering RNA (siRNA) is a potential method of gene silencing to target specific genes. Although the U.S. Food and Drug Administration (FDA) has approved multiple siRNA-based therapeutics, many biological barriers limit their use for treating diseases. Such limitations include challenges concerning systemic or local administration, short half-life, rapid clearance rates, nonspecific binding, cell membrane penetration inability, ineffective endosomal escape, pH sensitivity, endonuclease degradation, immunological responses, and intracellular trafficking. To overcome these barriers, various strategies have been developed to stabilize siRNA, ensuring their delivery to the target site. Chemical modifications implemented with nucleotides or the phosphate backbone can reduce off-target binding and immune stimulation. Encapsulation or formulation can protect siRNA from endonuclease degradation and enhance cellular uptake while promoting endosomal escape. Additionally, various techniques such as viral vectors, aptamers, cell-penetrating peptides, liposomes, and polymers have been developed for delivering siRNA, greatly improving their bioavailability and therapeutic potential.

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Section: Strategies For Engineering Sirna Therapeuticsmentioning

confidence: 99%

Section: Strategies For Engineering Sirna Therapeuticsmentioning

confidence: 99%

Engineering siRNA therapeutics: challenges and strategies

Ali Zaidi,

Fatima,

Ali Zaidi

et al. 2023

J Nanobiotechnol

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“…A30 was also used to deliver a set of cytotoxic siRNAs and inhibit growth in HER3 + breast cancer cells [280]. Recently, a novel RNA aptamer called HBR has been reported to inhibit HER3/ NRG interaction [281].…”

Section: In Preclinical Phasementioning

confidence: 99%

HER3 in cancer: from the bench to the bedside

Gandullo-Sánchez

Ocaña

Pandiella

2022

J Exp Clin Cancer Res

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The HER3 protein, that belongs to the ErbB/HER receptor tyrosine kinase (RTK) family, is expressed in several types of tumors. That fact, together with the role of HER3 in promoting cell proliferation, implicate that targeting HER3 may have therapeutic relevance. Furthermore, expression and activation of HER3 has been linked to resistance to drugs that target other HER receptors such as agents that act on EGFR or HER2. In addition, HER3 has been associated to resistance to some chemotherapeutic drugs. Because of those circumstances, efforts to develop and test agents targeting HER3 have been carried out. Two types of agents targeting HER3 have been developed. The most abundant are antibodies or engineered antibody derivatives that specifically recognize the extracellular region of HER3. In addition, the use of aptamers specifically interacting with HER3, vaccines or HER3-targeting siRNAs have also been developed. Here we discuss the state of the art of the preclinical and clinical development of drugs aimed at targeting HER3 with therapeutic purposes.

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