Commercializing the new frontier in DNA writing: Enzymatic synthesis

2020 ◽  
Vol 25 (4) ◽  
Author(s):  
Michael J. Kamdar ◽  
J. William Efcavitch

This article provides an overview of the emerging technology of enzymatic DNA synthesis, which holds the promise of making the business of writing DNA cost-effective, faster, sustainable, and more accurate compared to the traditional DNA synthesis method of phosphoramidite chemistry. Enzymatic DNA synthesis lends itself to various business models to realize the enormous opportunities across established and emerging industries that can be transformed with the reliable and affordable creation of long, high-quality, sequence specific DNA or, in the case of DNA data storage, the template-independent creation of DNA in nontoxic solutions without the need for post-synthesis processing. This review includes a discussion of potential verticals, such as life sciences – which includes gene editing, synthetic biology, precision medicine, DNA nanotechnology, and RNA vaccine development – as well as DNA data storage. Enzymatic DNA synthesis is being rapidly advanced to a commercial reality, with the first enzymatically synthesized DNA products to enter the market in the next year.


2021 ◽  
Author(s):  
Inbal Preuss ◽  
Zohar Yakhini ◽  
Leon Anavy

Storage needs represent a significant burden on the economy and the environment. Some of this can potentially be offset by improved density molecular storage. The potential of using DNA for storing data is immense. DNA can be harnessed as a high density, durable archiving medium for compressing and storing the exponentially growing quantities of digital data that mankind generates. Several studies have demonstrated the potential of DNA-based data storage systems. These include exploration of different encoding and error correction schemes and the use of different technologies for DNA synthesis and sequencing. Recently, the use of composite DNA letters has been demonstrated to leverage the inherent redundancy in DNA based storage systems to achieve higher logical density, offering a more cost-effective approach. However, the suggested composite DNA approach is still limited due to its sensitivity to the stochastic nature of the process. Combinatorial assembly methods were also suggested to encode information on DNA in high density, while avoding the challenges of the stochastic system. These are based on enzynatic assembly processes for producing the synthetic DNA. In this paper, we propose a novel method to encode information into DNA molecules using combinatorial encoding and shortmer DNA synthesis, in compatibility with current chemical DNA synthesis technologies. Our approach is based on a set of easily distinguishable DNA shortmers serving as building blocks and allowing for near-zero error rates. We construct an extended combinatorial alphabet in which every letter is a subset of the set of building blocks. We suggest different combinatorial encoding schemes and explore their theoretical properties and practical implications in terms of error probabilities and required sequencing depth. To demonstrate the feasibility of our approach, we implemented an end-to-end computer simulation of a DNA-based storage system, using our suggested combinatorial encodings. We use simulations to assess the performance of the system and the effect of different parameters. Our simulations suggest that our combinatorial approach can potentially achieve up to 6.5-fold increase in the logical density over standard DNA based storage systems, with near zero reconstruction error. Implementing our approach at scale to perform actual synthesis, requires minimal alterations to current technologies. Our work thus suggests that the combination of combinatorial encoding with standard DNA chemical synthesis technologies can potentially improve current solutions, achieving scalable, efficient and cost- effective DNA-based storage.



Author(s):  
Howon Lee ◽  
Daniel J. Wiegand ◽  
Kettner Griswold ◽  
Sukanya Punthambaker ◽  
Honggu Chun ◽  
...  

New storage technologies are needed to keep up with the global demands of data generation. DNA is an ideal storage medium due to its stability, information density and ease of readout with advanced sequencing techniques. However, progress in writing DNA is stifled by the continued reliance on chemical synthesis methods. The enzymatic synthesis of DNA is a promising alternative, but thus far has not been well demonstrated in a highly parallelized manner. Here, we report a novel multiplexed enzymatic DNA synthesis method using maskless photolithography. Rapid uncaging of Co2+ ions by patterned UV light activates Terminal deoxynucleotidyl Transferase (TdT) for spatially-selective synthesis on an array surface. Spontaneous quenching of reactions by the diffusion of excess caging molecules confines synthesis to light patterns and controls the extension length. We show that our multiplexed synthesis method can be used to store digital data by encoding 12 unique DNA oligonucleotide sequences with music from the 1985 Nintendo video game Super Mario Brothers™, which is equivalent to 84 trits or 110 bits of data.



2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Howon Lee ◽  
Daniel J. Wiegand ◽  
Kettner Griswold ◽  
Sukanya Punthambaker ◽  
Honggu Chun ◽  
...  

Abstract New storage technologies are needed to keep up with the global demands of data generation. DNA is an ideal storage medium due to its stability, information density and ease-of-readout with advanced sequencing techniques. However, progress in writing DNA is stifled by the continued reliance on chemical synthesis methods. The enzymatic synthesis of DNA is a promising alternative, but thus far has not been well demonstrated in a parallelized manner. Here, we report a multiplexed enzymatic DNA synthesis method using maskless photolithography. Rapid uncaging of Co2+ ions by patterned UV light activates Terminal deoxynucleotidyl Transferase (TdT) for spatially-selective synthesis on an array surface. Spontaneous quenching of reactions by the diffusion of excess caging molecules confines synthesis to light patterns and controls the extension length. We show that our multiplexed synthesis method can be used to store digital data by encoding 12 unique DNA oligonucleotide sequences with video game music, which is equivalent to 84 trits or 110 bits of data.



Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1072
Author(s):  
Raquel Cid ◽  
Jorge Bolívar

To date, vaccination has become one of the most effective strategies to control and reduce infectious diseases, preventing millions of deaths worldwide. The earliest vaccines were developed as live-attenuated or inactivated pathogens, and, although they still represent the most extended human vaccine types, they also face some issues, such as the potential to revert to a pathogenic form of live-attenuated formulations or the weaker immune response associated with inactivated vaccines. Advances in genetic engineering have enabled improvements in vaccine design and strategies, such as recombinant subunit vaccines, have emerged, expanding the number of diseases that can be prevented. Moreover, antigen display systems such as VLPs or those designed by nanotechnology have improved the efficacy of subunit vaccines. Platforms for the production of recombinant vaccines have also evolved from the first hosts, Escherichia coli and Saccharomyces cerevisiae, to insect or mammalian cells. Traditional bacterial and yeast systems have been improved by engineering and new systems based on plants or insect larvae have emerged as alternative, low-cost platforms. Vaccine development is still time-consuming and costly, and alternative systems that can offer cost-effective and faster processes are demanding to address infectious diseases that still do not have a treatment and to face possible future pandemics.



Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 390
Author(s):  
Frank Kowalzik ◽  
Daniel Schreiner ◽  
Christian Jensen ◽  
Daniel Teschner ◽  
Stephan Gehring ◽  
...  

Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail.



2021 ◽  
Vol 9 (6) ◽  
pp. 596
Author(s):  
Murugan Ramasamy ◽  
Mohammed Abdul Hannan ◽  
Yaseen Adnan Ahmed ◽  
Arun Kr Dev

Offshore vessels (OVs) often require precise station-keeping and some vessels, for example, vessels involved in geotechnical drilling, generally use Spread Mooring (SM) or Dynamic Positioning (DP) systems. Most of these vessels are equipped with both systems to cover all ranges of water depths. However, determining which system to use for a particular operational scenario depends on many factors and requires significant balancing in terms of cost-benefit. Therefore, this research aims to develop a platform that will determine the cost factors for both the SM and DP station-keeping systems. Operational information and cost data are collected for several field operations, and Artificial Neural Networks (ANN) are trained using those data samples. After that, the trained ANN is used to predict the components of cost for any given environmental situation, fieldwork duration and water depth. Later, the total cost is investigated against water depth for both DP and SM systems to determine the most cost-effective option. The results are validated using two operational scenarios for a specific geotechnical vessel. This decision-making algorithm can be further developed by adding up more operational data for various vessels and can be applied in the development of sustainable decision-making business models for OVs operators.





2015 ◽  
Vol 7 (1) ◽  
pp. 69-84 ◽  
Author(s):  
Yi Jie Tong ◽  
Wei Qi Yan ◽  
Jin Yu

With an increasing number of personal computers introduced in schools, enterprises and other large organizations, workloads of system administrators have been on the rise due to the issues related to energy costs, IT expenses, PC replacement expenditures, data storage capacity, and information security, etc. However, Application Virtualization (AV) has been proved as a successful cost-effective solution to solve these problems. In this paper, the analytics of a Virtual Desktop Infrastructure (VDI) system will be taken into consideration for a campus network. Our developed system will be introduced and justified. Furthermore, the rationality for these improvements will be introduced.



Silva Fennica ◽  
2020 ◽  
Vol 54 (4) ◽  
Author(s):  
Paula Jylhä ◽  
Pasi Rikkonen ◽  
Katri Hamunen

The size of Finnish wood harvesting enterprises has grown, and entrepreneurs have become responsible for various additional tasks, resulting in networking with other harvesting enterprises of various sizes and suppliers of supporting services, but the profitability of the wood harvesting sector has remained low. In the present study, the financial performance of 83 wood harvesting companies in Eastern and Northern Finland was evaluated, based on public final account data from a five-year period between 2013 and 2017. The factors underlying economic success were identified based on 19 semi-structured entrepreneur interviews. The Business Model Canvas framework was applied in the analyses. In particular, the smallest companies (with an annual turnover of less than 600 000 €) struggled with profitability. They showed increasing indebtedness, suffered from poor power in negotiations, had typically short-term contracts, and faced difficulties in retaining skilled operators. Most of the small companies were subcontractors of larger wood-harvesting companies. The better economic success of larger companies was likely based on their capacity to provide wood harvesting services in large volumes and supply versatile services, power in negotiations, and more cost-effective operations. The future development of wood harvesting seems to be polarised: larger enterprises are likely to continue growing, while the size of smaller enterprises has stabilised. Enhancing business management skills and practices is required in enterprises of all size groups.



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