Novel Modalities in DNA Data Storage

doi:10.1016/j.tibtech.2020.12.008

Trends in Biotechnology

Volume 39, Issue 10, October 2021, Pages 990-1003

https://doi.org/10.1016/j.tibtech.2020.12.008 Get rights and content

Highlights

Viable information storage in DNA is largely limited by cost and throughput.
Advances in synthesis and sequencing are key in driving adoption.
Different novel methods of storing information outside of nucleotide conversion are being explored.
The key workflows are not established, giving significant room for exploration.
The integration of molecular biology, engineering, and computing will drive further innovation.

The field of storing information in DNA has expanded exponentially. Most common modalities involve encoding information from bits into synthesized nucleotides, storage in liquid or dry media, and decoding via sequencing. However, limitations to this paradigm include the cost of DNA synthesis and sequencing, along with low throughput. Further unresolved questions include the appropriate media of storage and the scalability of such approaches for commercial viability. In this review, we examine various storage modalities involving the use of DNA from a systems-level perspective. We compare novel methods that draw inspiration from molecular biology techniques that have been devised to overcome the difficulties posed by standard workflows and conceptualize potential applications that can arise from these advances.

Section snippets

DNA as a Novel Information Storage Medium

Alternative methods of storing data are a burgeoning area of research due to the immense amount of data being generated every year. Existing storage formats are insufficient to accommodate this growth. Among various potential storage formats, ranging from storage in quantum bits to the metabolome [1., 2., 3., 4.], DNA has emerged as a promising material due to its immense storage density, its longevity, and the surfeit of tools developed for manipulating its properties.

The basic information

Encoding within Nucleotides

Most DNA storage methods store information in the form of nucleotide sequences (Figure 2A). The theoretical Shannon information capacity [12] of DNA is 2 bits/nt, although this limit is difficult to reach due to inherent errors in the DNA storage channel in the form of sequencing and synthesis error rates and biochemical constraints in sequence space [9,13]. As such, most work has been on encoding methods to optimize information redundancy. Other methods have explored ways such as using

Storage and Access

The process of storing information in DNA involves consideration of the environment in which the DNA generated is stored. The resilience of DNA is highly dependent on the storage medium in which it was kept and its inherent redundancy. Key traits of an appropriate storage medium include the ability to preserve the existing information, additional post-processing costs and steps, and physical space requirements. The ability of random access is also an important consideration in developing the

Reading

Advances in sequencing, the predominant form of information retrieval or ‘reading,’ drive the viability of DNA data storage. Predominant methods of reading DNA include sequencing by synthesis (SBS), along with third-generation sequencing methods involving single-molecule sequencing via nanopores or enzymatic well-based reactions, which have been reviewed extensively [69,70]. This section thus covers specific considerations of sequencing in DNA data storage and highlights advances made that can

Novel Applications of DNA Data Storage

The advent of new modalities reviewed in this paper has also led to the development of novel applications for DNA information storage beyond information archiving (Figure 1). One application is in the field of item authenticity and verification, whereby DNA that contains information on the veracity of an item is tagged onto the item itself. Multiple groups have developed ways of implementing DNA-based authentication, with tags being used in barcoding of oils [55], and for use in environmental

Concluding Remarks and Future Prospects

DNA has been the information store for biological information for millennia and has been the foundation of much work in modern biology. Now, its potential as a manipulatable material, coupled with the advent of technologies that can assist in this manipulation, has greatly expanded its applications. Data storage is but one of these applications. Novel advances in biotechnology have led to innovative approaches to storing data in DNA, and further innovations will only continue to increase as our

Acknowledgments

The authors thank Wen Xuan Er for her help in creation of the figures used in this paper. The authors are grateful for the support provided by the Synthetic Biology Initiative of the National University of Singapore (NUS) (DPRT/943/09/14), the Summit Research Program of the National University Health System (NUHSRO/2016/053/SRP/05), and an NUS startup grant (R-397-000-257-133).

Glossary

DNA computation: a field of research involving implementing computational processes on DNA strands.
DNA nanostructures: the concept of generating unique shapes and structures made solely from DNA by complementary base pairing of defined DNA strands.
Encoding and decoding: the algorithm used to convert binary information into another form, usually DNA nucleotide sequences.
Hachimoji DNA: a synthetic nucleic analog that comprises four novel nucleotides with unique base-pairing abilities.
Nanopores

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The necessity to record and store biological data is increasing in due course of time. However, it is quite difficult to understand biological mechanisms and keep a track of these events in some storage mediums. DNA (deoxyribonucleic acid) is the best candidate for the storage of cellular events in the biological system. It is energy efficient as well as stable at the same time. DNA-based writers and memory devices are continually evolving and finding new avenues in terms of their wide range of applications. Among all the DNA-based storage devices that employ enzymes like recombinases, nucleases, integrases, and polymerases, one of the most popular tools used for these devices is the emerging and versatile CRISPR Cas technology. CRISPR Cas is a prokaryotic immune system that keeps a memory of viral attacks and protects prokaryotes from potential future infections. The main aim of this short review is to study such molecular recorders and writers that employ CRISPR Cas technologies and obtain an in-depth overview of the mechanisms involved and the applications of these molecular devices.
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Long-term in vitro storage includes the following stages (Fig. 1): conversion of information into nucleotide sequences (encoding, stage 1), synthesis of oligos and formation of an oligotheca (stage 2), storage of an oligotheca under stable conditions (stage 3), obtaining of sufficient amount of informative DNA by amplification and their sequencing (stage 4), recovery of digital information from nucleotide sequences (decoding, stage 5). Some excellent reviews devoted to DNA data storage have recently been published (De Silva and Ganegoda, 2016; Akram et al., 2018; Panda et al., 2018; Ceze et al., 2019; Ping et al., 2019; Lim et al., 2021; Xu et al., 2021). However, the issue of encoding digital information by nucleotides has not been given proper attention.
In 2019, at the World Economic Forum, DNA data storage was indicated as one of the breakthroughs expected to radically impact the global socio-economic order. Indeed, dry DNA is a relatively stable substance and an extremely capacious information carrier. One gram of DNA can hold up to 455 exabytes, provided that one nucleotide encodes two bits of information. In this critical review, the main attention is paid to nucleinography, meaning the conversion of digital data into nucleotide sequences. The evolution and diversity of approaches intended for encoding data with nucleotides are demonstrated. The most noticeable examples of storing minor as well as considerable quantities of non-biological information in DNA are given. Some issues of DNA data storage are also reported.
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This novel storage architecture was achieved by encapsulating DNA using silica beads and mixing the beads with the material used to shape the target object. This essentially allows the ability to store information as DNA in any physical object and potentially opens up new areas for DNA storage, molecular identification, and DNA steganography [46]. Further exciting applications of DNA data storage can be seen in the rise of DNA computation.
Deoxyribonucleic acid (DNA) comprises four nucleotides and twenty amino acids (a combination of nucleotides) that generate living organisms’ structures. These discrete components, jointly with DNA characteristics and functions, allow understanding the DNA as a digital component. Thus, when DNA is considered an organic digital memory, it becomes a compelling data storage medium given its superior density, stability, energy efficiency, longevity, and lack of foreseeable technical obsolescence compared with conventional electronic media. Furthermore, various challenging experiments (described in this work) have demonstrated that digital information (regardless of its type, i.e., text, audio, video, image) can be written in DNA, stored, and accurately read. On the other hand, since nature has designed DNA with a tremendous capacity to store information, compression techniques (also described in this work) are required for appropriately managing this enormous quantity of information. Finally, we discuss a bit’s representation for nucleotides and amino acids due to DNA digital characteristics.
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Synthetic biology (SynBio) is a rapidly growing scientific discipline. In the Netherlands, various universities and companies are tackling a variety of opportunities and challenges within this field. In this perspective article, we review the current synthetic biology landscape in the Netherlands across academia, industry, politics, and society. Especially within Dutch academia there is an active, though only partially connected, research community involved in various domains of SynBio. Mostly supported by governmental funding, academic research is focusing on top-down synthetic biology, involving the engineering of, for example, bacteria and yeast for bioproduction, as well as bottom-up and cell-free synthetic biology aiming to understand life and build synthetic cells. There is also a large number of talented and motivated students interested in the field, exemplified by the participation and success of Dutch teams in the international iGEM synthetic biology competition. Commercial synthetic biology activities are taking place in various large industrial companies, as well as in start-ups and spin-offs, mostly divided over several ‘SynBio hubs’ in the Netherlands. However, the investment, regulatory and public-perception landscape is not yet optimal to stimulate entrepreneurial activities in SynBio. The Dutch and global society can further benefit from the large promise of SynBio through better integration of people active in the Dutch SynBio field, frequent political and public dialogue, and more attention towards regulatory issues. The recently founded Dutch synthetic biology association SynBioNL aims to contribute to realizing a positive impact on society by stimulating advances of the field in the Netherlands and beyond.
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Trends in Biotechnology

ReviewNovel Modalities in DNA Data Storage

Highlights

Section snippets

DNA as a Novel Information Storage Medium

Encoding within Nucleotides

Storage and Access

Reading

Novel Applications of DNA Data Storage

Concluding Remarks and Future Prospects

Acknowledgments

Glossary

A kilobyte rewritable atomic memory

Nat. Nanotechnol.

Storage of information using small organic molecules

ACS Cent. Sci.

Multicomponent molecular memory

Nat. Commun.

Principles of information storage in small-molecule mixtures

IEEE Trans. Nanobiosci.

Next-generation digital information storage in DNA

Science

Towards practical, high-capacity, low-maintenance information storage in synthesized DNA

Nature

Molecular digital data storage using DNA

Nat. Rev. Genet.

Reading and writing digital data in DNA

Nat. Protoc.

A characterization of the DNA data storage channel

Sci. Rep.

Demonstration of end-to-end automation of DNA data storage

Sci. Rep.

DNA storage: research landscape and future prospects

Natl. Sci. Rev.

A mathematical theory of communication

Bell Syst. Tech. J.

Probing the physical limits of reliable DNA data retrieval [published correction appears in Nat. Commun. (2020) 11, 1080]

Nat. Commun.

High information capacity DNA-based data storage with augmented encoding characters using degenerate bases

Sci. Rep.

Data storage in DNA with fewer synthesis cycles using composite DNA letters

Nat. Biotechnol.

Efficient and sequence-independent replication of DNA containing a third base pair establishes a functional six-letter genetic alphabet

Proc. Natl. Acad. Sci. U. S. A.

Hachimoji DNA and RNA: a genetic system with eight building blocks

Science

Catalog Technologies, Inc.

Rewritable digital data storage in live cells via engineered control of recombination directionality

Proc. Natl. Acad. Sci. U. S. A.

Permanent genetic memory with >1-byte capacity

Nat. Methods

Encoding information into polymers

Nat. Rev. Chem.

Large-scale de novo DNA synthesis: technologies and applications

Nat. Methods

Nucleic acid memory

Nat. Mater.

Synthetic DNA synthesis and assembly: putting the synthetic in synthetic biology

Cold Spring Harb. Perspect. Biol.

Low cost DNA data storage using photolithographic synthesis and advanced information reconstruction and error correction

Nat. Commun.

Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process

Nucleic Acids Res.

A high-throughput optomechanical retrieval method for sequence-verified clonal DNA from the NGS platform

Nat. Commun.

Toward a new paradigm of DNA writing using a massively parallel sequencing platform and degenerate oligonucleotide

Sci. Rep.

Highly selective retrieval of accurate DNA utilizing a pool of in situ-replicated DNA from multiple next-generation sequencing platforms

Nucleic Acids Res.

DNA nanotechnology

Nat. Rev. Mater.

Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation

Nat. Chem.

Nucleic acid-based nanotechnology

EMBO Rep.

Binary DNA nanostructures for data encryption

PLoS One

Addressable configurations of DNA nanostructures for rewritable memory

Nucleic Acids Res.

Digital data storage using DNA nanostructures and solid-state nanopores

Review
Novel Modalities in DNA Data Storage