A DNA nanodevice-based vaccine for cancer immunotherapy

Liu, Shaoli; Jiang, Qiao; Zhao, Xiao; Zhao, Ruifang; Wang, Yuanning; Wang, Yiming; Li, Jianbing; Shang, Yingxu; Zhao, Shuai; Wu, Tiantian; Zhang, Yinlong; Nie, Guangjun; Ding, Baoquan

doi:10.1038/s41563-020-0793-6

Cited by 414 publications

(374 citation statements)

References 31 publications

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“…20,21 DNA nanostructures have been used as delivery vehicles by selectively encapsulating drug molecules that can be released in a controlled fashion when the DNA nanostructure binds to specific cell types. 22,23 Additionally, these nanostructures can be used to study distance effects of receptor activation with nanometer precision [24][25][26][27][28] , enhance the cellular uptake of therapeutic drugs 29,30 , and are able to modulate drug release kinetics. 31,32 More specifically, it has been shown that compact nanostructures with a low aspect ratio are the preferred delivery vehicles for internalization 33 and that larger DNA origami structures exhibit a higher uptake efficiency.…”

Section: Introductionmentioning

confidence: 99%

Determinants of ligand-functionalized DNA nanostructure-cell interactions

Cremers

Rosier

Meijs

et al. 2021

Preprint

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Synthesis of ligand-functionalized nanomaterials with control over size, shape and ligand orientation, facilitates the design of tailored nanomedicines for therapeutic purposes. DNA nanotechnology has emerged as a powerful tool to rationally construct two- and three-dimensional nanostructures, enabling site-specific incorporation of protein ligands with control over stoichiometry and orientation. To efficiently target cell surface receptors, exploration of the parameters that modulate cellular accessibility of these nanostructures is essential. In this study we systematically investigate tunable design parameters of antibody-functionalized DNA nanostructures binding to therapeutically relevant receptors. We show that, although the native affinity of antibody-functionalized DNA nanostructures remains unaltered, the absolute number of bound surface receptors is lower compared to soluble antibodies and is mainly governed by nanostructure size and DNA handle location. The obtained results provide key insights in the ability of ligand-functionalized DNA nanostructures to bind surface receptors and yields design rules for optimal cellular targeting.

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Section: Introductionmentioning

confidence: 99%

Determinants of ligand-functionalized DNA nanostructure-cell interactions

Cremers

Rosier

Meijs

et al. 2021

Preprint

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“…The recently reported construction of an antitumor vaccine based on the nanotemplating of multiple elements onto DNA origami is a first proof of concept, albeit for a vastly different class of target. [ 92 ] Nevertheless, the full modularity of this approach, where different antigens and immune modulators can be linked together in nearly any combination, is particularly enticing for viruses, which can mutate from season to season and present new strains or serotypes with little warning or time to react.…”

Section: Discussionmentioning

confidence: 99%

“…These two strategies of modular antigen adjuvant proximity coupling and high‐density adjuvant clustering were finally combined in a study by Liu et al, where a multifunctional DNA nanostructure was generated as a synthetic, antitumor vaccine (see Figure 7d). [ 92 ] Similar to the earlier study by Schüller et al, a barrel‐shaped DNA nanostructure itself was assembled via the DNA origami method; however, this case included several critical differences. Here, stimulatory adjuvant molecules (both CpG motifs and dsRNA segments to activate both TLR3 and TLR9) as well as the tumor antigens (synthetically produced peptide segments) were all arranged in the inner surface of the barrel structure, which was held closed by a pH‐sensitive dsDNA‐locking system.…”

Section: Dna Nanostructures For Pathogen Inhibitionmentioning

confidence: 99%

DNA Nanostructures in the Fight Against Infectious Diseases

Smith

Keller

2021

Advanced NanoBiomed Research

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The ongoing COVID-19 pandemic has once more led to the realization that humanity is dangerously ill prepared for fighting the threats associated with epidemic outbreaks of infectious diseases. COVID-19 is only the latest in a long list of viral diseases, including SARS, [1] MERS, [2] Zika, [3] Ebola, [4] and Nipah, [5] that emerged as severe threats to public health in the past two decades and that continue to threaten human lives. However, also diseases that have plagued humanity for centuries still present a severe burden. For instance, the 20th century has seen three influenza pandemics with death tolls in the millions [6] and the seasonal flu still kills on average an estimated 389 000 people each year. [7] Furthermore, due to the global rise of antibiotic resistance in the past few decades, bacterial infections have once again become a severe threat to human health. [8] In 2015, about 670 000 patients in the EU alone suffered from infections with antibiotic-resistant strains of eight bacterial pathogens, resulting in 33 000 deaths. [9] The situation in the US is similar, with an estimated 23 000 deaths each year as a direct result of more than 2 million multidrug-resistant infections. [10] In low-and middle-income countries with limited ability to pay for second-line drugs, antibiotic resistance results in even higher mortality rates. In 2010, about 38 000 deaths in Thailand alone were attributed to infections with only five antibiotic-resistant bacteria. [11] In India, it is estimated that about 60 000 neonatal deaths each year result from antibiotic-resistant bacterial infections. [8] More recently, the worldwide emergence of antifungal resistance has raised grave concerns as well, [12] as invasive fungal infections are responsible for at least 2 million life-threatening

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“…Their experimental results have clearly shown that DNA nanodevices with antigens and adjuvants can realize effective and intelligent cancer immunotherapy by inhibiting the tumor growth, metastasis and recurrence (Figure 4). [42] At present, most of the intelligent DNA-based protein assemblies with therapeutic functions are stimulus-responsive, and their 'intelligence' level is only sufficient to respond to the presence or absence of a specific target. However, the development of personalized treatment tools has raised higher requirements for the capabilities of nanorobots.…”

Section: Intelligent Drug Deliverymentioning

confidence: 99%

“…d) Effect of inhibiting tumour metastasis and recurrence with the nanodevice vaccine. Reproduced from Ref [42]. with permission from Nature Publishing Group.…”

mentioning

confidence: 99%

DNA‐Guided Programmable Protein Assemblies for Biomedical Applications

Han

2021

ChemPlusChem

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While the protein assemblies have been found widely existing and playing significant roles in biological systems, their imitation and re‐construction is further boosting more applications in biomedical research, such as enzymatic reaction regulation, sensing, and biomedicine. DNA nanotechnology provides a programmable strategy for the fabrication of nanostructures with unprecedented accuracy on the nanoscale. By linking the DNA nanotechnology with proteins of different functions, the precise construction of DNA‐guided protein assemblies can be achieved for various biomedical applications. This minireview summarizes the recent advances in the programmable protein assemblies on DNA nanoplatforms and discusses the outlook of DNA‐guided protein assemblies in the biomedical research.

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A DNA nanodevice-based vaccine for cancer immunotherapy

Cited by 414 publications

References 31 publications

Determinants of ligand-functionalized DNA nanostructure-cell interactions

Determinants of ligand-functionalized DNA nanostructure-cell interactions

DNA Nanostructures in the Fight Against Infectious Diseases

DNA‐Guided Programmable Protein Assemblies for Biomedical Applications

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