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Watson–Crick base pairing rules provide a powerful approach for engineering DNA‐based nanodevices with programmable and predictable behaviors. In particular, DNA strand displacement reactions have enabled the development of an impressive repertoire of molecular devices with complex functionalities. By relying on DNA to function, dynamic strand displacement devices represent powerful tools for the interrogation and manipulation of biological systems. Yet, implementation in living systems has been a slow process due to several persistent challenges, including nuclease degradation. To circumvent these issues, researchers are increasingly turning to chemically modified nucleotides as a means to increase device performance and reliability within harsh biological environments. In this review, we summarize recent progress toward the integration of chemically modified nucleotides with DNA strand displacement reactions, highlighting key successes in the development of robust systems and devices that operate in living cells and in vivo. We discuss the advantages and disadvantages of commonly employed modifications as they pertain to DNA strand displacement, as well as considerations that must be taken into account when applying modified oligonucleotide to living cells. Finally, we explore how chemically modified nucleotides fit into the broader goal of bringing dynamic DNA nanotechnology into the cell, and the challenges that remain.

This article is categorized under:

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Vaccines are considered one of the most significant medical advancements in human history, as they have prevented hundreds of millions of deaths since their discovery; however, modern travel permits disease spread at unprecedented rates, and vaccine shortcomings like thermal sensitivity and required booster shots have been made evident by the COVID‐19 pandemic. Approaches to overcoming these issues appear promising via the integration of vaccine technology with biomaterials, which offer sustained‐release properties and preserve proteins, prevent conformational changes, and enable storage at room temperature. Sustained release and thermal stabilization of therapeutic biomacromolecules is an emerging area that integrates material science, chemistry, immunology, nanotechnology, and pathology to investigate different biocompatible materials. Biomaterials, including natural sugar polymers, synthetic polyesters produced from biologically derived monomers, hydrogel blends, protein–polymer blends, and metal–organic frameworks, have emerged as early players in the field. This overview will focus on significant advances of sustained release biomaterial in the context of vaccines against infectious disease and the progress made towards thermally stable “single‐shot” formulations.

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

To overcome the challenge of lysosomal degradation of material in cells, we developed a carrier using chemical synthesis to successfully bypass the endosomal trap and deliver therapeutic materials directly into the cytoplasm of cells.

Qβ VLP simplified assembly approach uses the positively charged Rev tag to interact electrostatically with the negatively charged RNAs. This system exploits the known hairpins produced in the coat protein sequence to template the assembly of the full viral capsid.

Needle-and-syringe-based delivery has been the commercial standard for vaccine administration to date. With worsening medical personnel availability, increasing biohazard waste production, and the possibility of cross-contamination, we explore the possibility of biolistic delivery as an alternate skin-based delivery route. Delicate formulations like liposomes are inherently unsuitable for this delivery model as they are fragile biomaterials incapable of withstanding shear stress and are exceedingly difficult to formulate as a lyophilized powder for room temperature storage. Here we have developed a approach to deliver liposomes into the skin biolistically—by encapsulating them in a nano-sized shell made of Zeolitic Imidazolate Framework-8 (ZIF-8). When encapsulated within a crystalline and rigid coating, the liposomes are not only protected from thermal stress, but also shear stress. This protection from stressors is crucial, especially for formulations with cargo encapsulated inside the lumen of the liposomes. Moreover, the coating provides the liposomes with a solid exterior that allows the particles to penetrate the skin effectively. In this work, we explored the mechanical protection ZIF-8 provides to liposomes as a preliminary investigation for using biolistic delivery as an alternative to syringe-and-needle–based delivery of vaccines. We demonstrated that liposomes with a variety of surface charges could be coated with ZIF-8 using the right conditions, and this coating can be just as easily removed—without causing any damage to the protected material. The protective coating prevented the liposomes from leaking cargo and helped in their effective penetration when delivered into the agarose tissue model and porcine skin tissue.

We can alter the release kinetics of highly stabilized biomacromolecules in both skin and plant tissues to allow for either instant release or slow release simply by changing the typeof gas used in a pneumatic delivery jet.