Recently, ‘scaffolded DNA origami’ (DO) has emerged as one of the most promising assembly techniques with many applications. Its core is a long DNA molecule scaffolding through simplified DNA structures for advanced applications. Structures from DNA origami are lightweight, small, and modified for controlled applications. It provides various construction possibilities, gives nanoscale precision, creates dynamic nanostructures, and accurately tunes metabolic and non-metabolic interactions. Recent technological progress paves the way for future applications such as molecular diagnosis, drug delivery, therapeutic applications, fluorescence imaging, superconductive materials, advanced renewable materials, and nanorobots.
DNA Origami and its Areas of Application
Origami (ori means “folding“& kami means “paper“) is a term associated with Japanese culture and the art of paper folding. Like origami, it is related to the folding of DNA.
The technology involves designing and building multi-dimensional nanoscale DNA with predetermined characteristics.
Figure 1 shows the conversion of cyclic ssDNA into DNA Origami, wherein long single-stranded DNA is folded into the desired shape by many short DNAs, termed “staple.” Stable strands are further connected on the various sides depending on the origami structure using a different process.
It has applications in several therapeutic and non-therapeutic domains, including –
- Delivery: Drugs, proteins, enzymes, antibodies, and nucleic acids
- Therapy: Gene therapy, chemotherapy, immunotherapy, and phototherapy
- Sensing: Bio-sensing (nucleic acid sensing and protein sensing), fluorescence sensing, and chemical Sensing
- Regulation of Reactions – Enzymatic reaction, protein substrate reaction, gene reaction, and metabolic pathway cascade reaction
- Studies of biomolecule, light, energy, and microscopy
- Diagnosis and detection – Tumours and virus
- Nanotechnology-Nanofabrication, nano-photonics, nano-electronics, and nano-robots
Recent Technology Trends
Globally, many research organizations are working on improving origami techniques and expanding their applications in the therapeutic and diagnostic areas, especially in drug delivery and fluorescence technology. Some of the new innovative improvements utilizing DNA origami are –
- Octahedral-shaped DNA origami – can be used in making highly superconductive materials. This novel technique might enhance the speed and accuracy of quantum computers and ultrasensitive magnetic field sensors for medical and geophysical applications.
- Icosahedral Nano capsules help prevent infection by containing triangular DNA origami that traps viruses such as hepatitis, adeno-associated viruses, and coronaviruses.
- Self-assembled DNA origami with a programmable geometry can control the distance between the antigens. This helps by spatially placing antigens at an equivalent distance to enable the antibodies to interact with them, allowing it for greater control over the affinity maturation process for vaccine development and therapeutics.
- Allosteric DNA-origami Nano-machine is controlled by DNA input to enable the programmable control of DNA-Network, molecular, and metabolic pathways.
- A molecular diagnostic device with DNA origami, gold nanoparticle, and a fluorescence marker that can detect a single molecule and identify the drug resistance disease. This method can detect a single molecule using a small, compact optical device. It helps hold the gold nanoparticles in place. Placing a fluorescent dye at the captured target enhances the detectable long-wave fluorescence radiation multiple times.
- DNA origami-based Digital Nucleic Acid Memory (dNAM) technology can encode and decode the image data. This opens the door for the future of DNA origami data storage material.
A Look at the Prospects DNA Origami
Researchers are working on creating a universal scaffolding technique for various next-gen applications. Each year, the number of unique origami structures with novel applications grows exponentially.
The possible next-generation applications of DNA origami in the near future are endless, and a few of them are –
- Advanced Drug Delivery — It offers a highly sophisticated therapeutic delivery system because of its tiny size, high designability, programmability, and multiple load-carrying features.
- Precision Therapy — It presents antigens, target-specific medication delivery, and infectious organism trapping. One can effectively control ailments by utilizing the programmable control and regulation of metabolic reactions offered by DNA origami. This might lead to the revolutionary precision treatment of cancer, infectious diseases, and other generic disorders.
- Ultra-level Diagnosis – The fluorescent technology, biosensor, and single molecule bio-sensing approach of DNA origami detect the biomarker in low-concentration samples, improve the bio-sensing device’s performance, and decrease the diagnostic cost and time.
- Nanopore Sequencing – Nanopore origami, using fluorescence and encapsulation, provides a better platform for DNA sequencing to improve the quality and speed of diagnosing fast-spreading pandemic diseases.
- Sustainable Data Storage – DNA is a plentiful natural resource. DNA’s modest size and ATGC bases allow it to store much information. Scientists successfully stored and retrieved the data in DNA origami structures. It offers a variety of future long-term data storage platform development options.
- Self-Assembled Electronic Components –It finds applications in 2D/3D arrays, nanoelectronic circuits, small transistors, and serves as the building blocks of computers. In the future, self-assembled compact electronic components could be possible.
Market Trends & Major Competitors
Key players in the DNA origami market are increasing their R&D activities and efforts to develop novel products and services. Below are some of the latest developments in DNA origami by significant players.
The company, TECNALIA, took the DeDNAed initiative to develop the biosensor’s DO-based analytical platform. This platform allows the precise location of these sensors with nanometric resolution, required for better detection by surface-improved Raman spectroscopy. This platform has advantages such as sensitivity, versatility, and ultra-fast through an optical approach.
SprinD committed with Tilibit Nanosystems to develop nano-machines and biochips using DO for precise disease diagnosis.
A research team from Ohio State University was awarded $2 million by the National Science Foundation (NSF) Emerging Frontiers in Research and Innovation (EFRI) program to develop DNA origami-based nano-devices to control cellular function and monitor gene expression.
Aalto University scientists got funds from the European Research Council for developing remote-controlled nanoscale artificial molecular machines using DO.
Conclusion
DNA origami nanostructures are adaptable nanostructures with many biological uses due to their size, the availability of sophisticated chemical and enzymatic techniques to alter their nucleotides and functions, and their biocompatibility. DO-based nanostructures have been employed as platforms for spatially controlled enzyme cascades, investigation of dynamic molecular events, triggered cargo release, immune stimulation, and molecular chips for label-free RNA detection. However, the lack of adequate ssDNA scaffolds is the main obstacle to developing DO structures.
Designing complex structures with DO requires manual adjustment due to additional constraints, including DNA geometry and sense/antisense pairing. Utilizing complete genomes as scaffolds, such as the commonly used M13, restricts its designs to discrete dimensions. Alternative methods for building structures at the nanoscale include the recently established “molecular canvas” concept and single-stranded “DNA bricks.”
However, recent innovations have represented promising biotechnological applications. These include automated routing algorithms, analysis of effective folding pathways, and the creation of finite-size wireframe nanostructures with great complexity and programmability, which result in improved technology. Recent development emphasizes its potential for encapsulating igens/probes for therapy, detection, or biosensors. Its lithography can pattern micrometer-scale structures and become a promising tool for developing solid-state devices with precise and programmable surface interactions.