Cambridge, MA, U.S.
A Paper-Based Genetic Function Library for Space Travel
2026
How To Grow (Almost) Anything, MIT Media Lab
How To Grow (Almost) Anything, MIT Media Lab
Individual Project
Yanchen Shen (Harvard GSD MDes Mediums ‘27)
SECTION 1:
ABSTRACT
Long-duration space travel will require compact, low-power, and cold-chain-free ways to preserve biological instructions and activate useful functions away from Earth. My project, Off-World Archive, proposes a dry, paper-based DNA library that stores genetic programs for space-relevant proteins, enables recovery of those DNA templates, and supports on-demand cell-free protein production during space travel. The long-term vision is not simply to store information in DNA, but to store deployable biological functions as paper-based genetic “program cards” for use in remote or spaceflight settings. I originally intended to test a functional protein construct encoding SspCA, a thermostable carbonic anhydrase relevant to carbon dioxide processing, but that DNA order did not arrive in time. Therefore, the completed class validation became Aim 0.5: a feasibility test for whether synthetic DNA data fragments can be stored dry on paper, recovered, cleaned up, and remain readable by endpoint PCR.
The broader project includes a next-stage Aim 1 focused on SspCA, a thermostable carbonic anhydrase relevant to carbon dioxide processing. For this class, I completed Aim 0.5 as a pilot study to test whether paper-stored DNA fragments can be recovered and remain molecularly readable. I used untreated cellulose paper and APTMS-treated paper as storage substrates, recovered DNA by salt elution and column cleanup, amplified payload regions from two synthetic fragments, and visualized the products on a 2% E-Gel EX agarose gel. My hypothesis was that DNA stored on paper would remain molecularly readable after short-term dry storage and recovery. The expected outcome was correctly sized PCR bands from recovered paper samples and clean negative controls.
This Aim 0.5 result validates the archive-readability layer of the project, while Aim 1 remains the future step: replacing the DNA-data payload with a space-relevant functional protein construct and demonstrating cell-free protein activity after paper recovery.
SECTION 2:
PROJECT AIMS
— Build and validate the paper-based genetic function archive pipeline
The first aim of my final project is to build a paper-based DNA storage and recovery workflow for an off-world genetic function archive by utilizing Benchling-based DNA construct design, Twist-synthesized DNA fragments, APTMS-treated and untreated cellulose paper, dry DNA loading, salt-based DNA recovery, DNA cleanup, endpoint PCR, E-Gel electrophoresis, and a planned cell-free expression workflow for an SspCA protein construct.
This aim includes Aim 0.5, the completed in-class pilot experiment, which tested whether synthetic DNA fragments stored on paper could be recovered and remain molecularly readable by PCR. The full Aim 1 extends this pilot toward the functional goal of recovering an SspCA-encoding DNA construct from paper, expressing it in a cell-free system, and measuring whether the recovered DNA can still produce functional carbonic anhydrase activity.
— Test the archive under simulated International Space Station (ISS) conditions
The second aim is to develop a follow-up experimental system that tests paper-stored functional DNA under conditions that approximate the International Space Station environment, including longer dry-storage time, temperature variation, humidity stress, limited handling volume, and potentially radiation-relevant stress testing through available ground-based proxies.
This aim would compare untreated paper, APTMS-treated paper, and improved paper-cartridge geometries by measuring DNA recovery, PCR/qPCR readability, cell-free expression output, and SspCA activity after storage. The purpose of Aim 2 is to move beyond a room-temperature classroom feasibility test and begin asking whether the archive format still works under operational constraints relevant to space biology workflows.
— Develop an off-world paper-based DNA library for on-demand protein production
The third aim is to develop a scalable paper-based DNA library containing multiple genetic programs for proteins useful in space-travel contexts, such as carbon dioxide processing enzymes, biosensing proteins, repair enzymes, nutrient-related proteins, or emergency-use synthetic biology tools. In the long term, the Off-World Archive would function as a compact dry genetic library that stores DNA programs on paper or paper-like cartridges, allows astronauts or autonomous systems to recover selected constructs, and enables on-demand cell-free protein production without maintaining living engineered organisms or cold-chain inventories.
If fully realized, this project could create a new workflow for storing biological function as dry DNA instructions, shifting space biotechnology from transporting finished biological materials toward transporting readable and reactivatable genetic programs.
SECTION 3:
BACKGROUND
DNA data storage is usually framed as a pipeline of digital encoding, DNA synthesis, preservation, retrieval, sequencing, and decoding. Reviews of the field emphasize that DNA stability is not a secondary issue but a central design constraint because DNA is chemically degradable and its lifetime depends on humidity, temperature, radiation, handling, storage format, and access frequency [3]. Twist Bioscience and others describe DNA storage as an emerging archival technology because DNA has high physical density and potentially low energy needs, but practical systems still require reliable preservation and readout [17]. My project borrows this DNA-storage logic but shifts the final vision from passive data storage to functional genetic storage: storing DNA templates that can later drive protein production.
Two peer-reviewed references are especially important. First, Liu et al. demonstrated sustainable DNA data storage on cellulose paper, reporting that digitally encoded DNA pools could be stored on cellulose paper through electrostatic adsorption, dried, and retrieved repeatedly [1]. Their work supports the idea that cellulose paper is a plausible low-cost substrate for dry DNA preservation rather than only a disposable assay material. Second, Zhou et al. developed a one-step APTMS surface modification method to graft DNA codes onto paper, showing that positively charged APTMS-modified paper interacts with negatively charged DNA and can improve DNA immobilization efficiency [2]. This paper directly informed my APTMS-paper condition, where APTMS treatment was used to test whether a modified cellulose surface could support stronger DNA retention or recovery than untreated paper.
Other literature shaped my interpretation of the results. Zou et al. showed that untreated cellulose-based paper can rapidly capture nucleic acids and yield amplification-ready material [4], which explains why untreated paper in my experiment was not expected to be a zero-signal control. FTA-card literature also shows that paper-like matrices can preserve DNA at ambient temperature for molecular analysis over long periods [5]. Together, these papers suggest that a short-term experiment may show readability in both treated and untreated paper, while longer stress tests are required to determine which matrix is more robust.
For the planned functional layer, SspCA is my first protein target because carbonic anhydrases catalyze CO2 hydration, and SspCA from Sulfurihydrogenibium yellowstonense has been studied as a thermostable carbonic anhydrase [6]. Spacecraft already require artificial air revitalization systems, and NASA describes CO2 removal and oxygen recovery as central functions within environmental control and life support systems [7-9]. The planned SspCA aim would not replace spacecraft life support hardware, but it would provide a tractable biological function prototype for asking whether paper-stored DNA can be recovered and used to make a useful enzyme in a cell-free system.
DOI: 10.1021/acs.analchem.0c00317
The novelty of Off-World Archive is the combination of paper-based DNA preservation, DNA data-storage logic, and cell-free genetic function production in a space-relevant design frame. Existing DNA storage demonstrations often focus on sequence recovery or digital file decoding, while my long-term concept asks whether the stored DNA can remain biologically useful as a template for protein production. The completed Aim 0.5 experiment is therefore intentionally modest: it validates the molecular-readability layer before the project moves into functional protein expression. This staged approach is innovative because it treats DNA on paper as a genetic function library, not only as an information archive.
The project also reframes paper not only as a low-cost substrate, but as a customizable archive form factor. The DNA-loaded paper library could be fabricated and indexed on Earth through automated spotting, drying, and packaging workflows. The space-specific challenge is the later readout and use of the archive: in microgravity, loose paper discs may be difficult to handle, recover from, or keep contamination-free. This suggests two design paths: building sealed accessories around the paper, such as capillary recovery cartridges, or redesigning the paper itself so that its geometry, wettability, and retrieval interface are optimized for use in space.
Long-duration missions beyond low Earth orbit will not be able to rely on frequent resupply of every biological reagent, protein, sensor, or medical material. NASA already investigates space synthetic biology and on-demand biomanufacturing approaches such as BioNutrients, where dried biological systems are activated with water to produce useful compounds [8]. A dry DNA-function library would be a complementary strategy: instead of storing living engineered cells for every function, the archive would store DNA templates that can be activated in modular cell-free reactions. Such a system could reduce mass, support late-binding of mission functions, and allow a small physical library to encode many proteins.
The project matters scientifically because it tests the first step of that idea: can DNA be stored on a simple material and still be read after recovery? It matters technically because paper-based DNA storage could be lower cost, easier to distribute, and easier to automate than many encapsulated or refrigerated systems. It matters for synthetic biology because it connects DNA construct design with material storage and functional readout, rather than treating sequence design and storage hardware separately. In the near term, the project produces an educational proof-of-principle for DNA readability after paper storage. In the long term, it could contribute to compact, low-power biological infrastructure for field science, remote laboratories, and off-world missions.
This project stores synthetic DNA as recoverable biological instructions, so the main ethical concern is dual use: the same workflow that stores useful protein-coding sequences could also store harmful or unauthorized sequences. For this reason, the project should use only screened, non-pathogenic DNA designs and maintain clear records of sequence origin, construct purpose, and sample identity.
A second concern is responsible framing. Aim 0.5 only showed that short paper-stored DNA fragments remained PCR-readable after short-term storage; it did not prove long-term stability, superiority of APTMS paper, or functional protein production. Future versions should clearly separate demonstrated results from proposed applications, especially in space-relevant contexts.
Responsible practice for this project includes using benign synthetic constructs, documenting all DNA designs and controls, following synthesis-screening rules, avoiding overclaiming experimental results, and designing future archive systems with contamination control, access control, and mission safety in mind.
SECTION 4:
EXPERIMENTAL DESIGN, TECHNIQUES, TOOLS, AND TECHNOLOGY
The first step was to convert the short messages “HELLO WORLD” and “HTGAA” into DNA-encoded payloads. These encoded payloads became Fragment A and Fragment B, allowing Aim 0.5 to test whether text-derived DNA data could be stored on paper, recovered, and still read molecularly by PCR.
DNA Code Translator:
Text
→ ASCII / UTF-8
→ Binary
→ 2-bit mapping
→ constraint encoding (avoid AAAA)
→ add index + redundancy
→ DNA sequence
For Aim 0.5, use T7-sfGFP_DataFragment_A_v1 and T7-sfGFP_DataFragment_B_v1, both gene fragments ordered from Twist with sequence-defined payload regions.
Fragment A and Fragment B are designed around the encoded payloads, including primer-binding regions that allow the recovered DNA to be tested by endpoint PCR.
Expected result: two synthetic DNA fragments with shared expression architecture and distinguishable payload PCR outputs.
Resuspend dry Twist gene fragments to 10 ng/uL stocks, prepare Fresh-A and Fresh-B no-paper controls, and prepare paper-loading mixes.
Expected result: known input DNA concentration and positive controls for later PCR.
Use untreated cellulose paper as the baseline substrate and APTMS-treated cellulose paper as the modified condition, building on literature showing APTMS-mediated DNA immobilization on paper.
Expected result: paired untreated and aminosilane-treated paper storage samples.
Spot equal volumes of Fragment A or Fragment B loading mix onto the assigned paper pieces, with approximately 30 ng DNA per disc in the completed experiment.
Expected result: matched A-U, A-P, B-U, and B-P paper samples
For the completed course pilot, storage was short-term (24h); for future work, use a time course such as 1 week, 1 month, and accelerated humidity/temperature stress.
Expected result: dry archive samples ready for recovery.
Use 10 mM Tris-HCl plus 0.5 M NaCl recovery buffer, incubate the paper pieces, and transfer recovered eluate into clean tubes.
Expected result: DNA-containing recovery solution.
Use a DNA cleanup column such as Zymo DNA Clean & Concentrator-5 to remove salts and concentrate the eluate.
Expected result: approximately 10 uL of cleaned DNA suitable for PCR.
Set up Payload PCR reactions using Thermo Scientific 2X Phusion Master Mix with HF Buffer, qPCR_Payload_F/R primers, and 2 uL template.
Expected result: amplification only in template-containing positive samples.
Use 98 C denaturation, 35 cycles, 60 C annealing, 72 C extension, and final extension.
Expected result: short payload amplicons from fresh and paper-recovered DNA.
Load ladder, fresh controls, APTMS-paper samples, untreated-paper samples, NTC, and water lanes.
Expected result: A samples near 100 bp and B samples between 100 and 200 bp.
Resuspend dry Twist gene fragments to 10 ng/uL stocks, prepare Fresh-A and Fresh-B no-paper controls, and prepare paper-loading mixes.
Expected result: Score whether fresh controls amplify, whether recovered paper samples amplify, whether A and B migrate differently, and whether negative controls are clean.
Expected result: a presence/absence readability dataset.
Fresh-A, A-P1, and A-U1 produced bands near the expected Fragment A payload size of approximately 94 bp, while Fresh-B, B-P1, and B-U1 produced bands near the expected Fragment B payload size of approximately 166 bp. The NTC and water-only lanes showed no clear bands, suggesting that the PCR and gel readout were not dominated by obvious contamination. Overall, the result supports the conclusion that DNA stored on both APTMS-treated and untreated paper could be recovered and remained PCR-readable after short-term dry storage.
However, this gel should be interpreted as a qualitative readability result, not as a quantitative comparison of storage performance. Both APTMS-treated and untreated paper samples produced visible bands, so the experiment does not yet demonstrate that APTMS treatment outperformed untreated paper. The storage time was also short, which may explain why the difference between treated and untreated paper was not visually strong. In addition, endpoint PCR can reach a plateau phase, so band brightness is not a reliable measure of original DNA recovery. The ladder used was also not ideal for precise sizing below 100 bp, and the experiment did not include sequencing or full DNA data decoding. Therefore, Aim 0.5 validates the basic storage–recovery–PCR readability workflow, but future work should use longer storage times, qPCR or digital PCR, and sequence verification to quantify recovery and confirm data integrity.
Use T7-SspCA_WT_HisTag_SpaceOpt_v1, recovered from paper, as a cell-free expression template; measure carbonic anhydrase function with a CO2 hydration assay.
Expected result: movement from DNA readability to protein function.
SECTION 5:
RESULTS AND QUANTITATIVE EXPECTATIONS
I validated the archive-readability layer of Off-World Archive. Specifically, I tested whether synthetic DNA fragments stored on untreated or APTMS-treated paper could be recovered and amplified by endpoint PCR. This validation is Aim 0.5: a DNA data-storage feasibility experiment that supports the larger project by proving that paper-recovered DNA can still serve as a molecular template. It does not yet prove long-term preservation, digital decoding, or cell-free protein production.
Unexpected challenges, limitations, and alternatives
The first challenge was conceptual: the completed Aim 0.5 experiment validates DNA readability, but it does not fully describe the Off-World Archive vision. It is a necessary layer of the project, not the final function-storage demonstration. The second challenge was analytical: endpoint PCR and gel electrophoresis are excellent for visible proof-of-readability, but they are weak for comparing recovery efficiency between paper treatments. This means that similar band intensity in treated and untreated samples should not be overinterpreted. A stronger follow-up would use qPCR or digital PCR to compare recovered copy number and include longer storage intervals, humidity stress, temperature stress, and possibly radiation simulation.
A major reflection from the experiment is that the storage time was likely too short to reveal a strong difference between APTMS-treated and untreated paper. If both paper types can retain enough DNA for PCR after short storage, a longer time-course is needed to ask which substrate better protects against degradation or loss. Another reflection is that the manual workflow involved many repeated pipetting, labeling, and transfer steps. In a large DNA library context, this repetitive process is a strong candidate for liquid-handling automation, and in a spaceflight context it suggests that the archive should become a sealed cartridge or capillary device rather than loose paper pieces.
For the space-relevant version of the project, the physical archive design matters as much as the DNA chemistry. Microgravity changes liquid handling; droplets do not behave as they do on a benchtop, and sealed capillary or microfluidic designs may be necessary to control recovery liquids. Radiation and long-term storage stability also become central design constraints, especially outside low Earth orbit.
SECTION 6:
ADDITIONAL INFORMATION
REFERENCES
[1] Liu, Q., Wei, Y., Wang, Z., et al. (2023). Sustainable DNA Data Storage on Cellulose Paper. Small Methods, e2201610. https://www.twistbioscience.com/resources/publication/sustainable-dna-data-storage-cellulose-paper
[2] Zhou, W., Feng, M., Valadez, A., & Li, X. (2020). One-Step Surface Modification to Graft DNA Codes on Paper. Analytical Chemistry, 92, 7045-7053. https://pubs.acs.org/doi/10.1021/acs.analchem.0c00317
[3] Matange, K., Tuck, J. M., & Keung, A. J. (2021). DNA stability: a central design consideration for DNA data storage systems. Nature Communications, 12, 1358. https://www.nature.com/articles/s41467-021-21587-5
4] Zou, Y., Mason, M. G., Wang, Y., et al. (2017). Nucleic acid purification from plants, animals and microbes in under 30 seconds. PLOS Biology, 15(11), e2003916. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2003916
[5] Rajendram, D., Ayenza, R., Holder, F. M., Moran, B., Long, T., & Shah, H. N. (2006). Long-term storage and safe retrieval of DNA from microorganisms for molecular analysis using FTA matrix cards. Journal of Microbiological Methods, 67(3), 582-592. https://researchportal.ukhsa.gov.uk/en/publications/long-term-storage-and-safe-retrieval-of-dna-from-microorganisms-f/
6] Di Fiore, A., et al. Structural and biochemical studies of SspCA from Sulfurihydrogenibium yellowstonense, a thermostable carbonic anhydrase. https://pmc.ncbi.nlm.nih.gov/articles/PMC6493269/
[7] NASA. Environmental Control and Life Support Systems (ECLSS). https://www.nasa.gov/reference/environmental-control-and-life-support-systems-eclss/
[8] NASA Ames. Synthetic Biology and Space Synthetic Biology resources, including BioNutrients and CO2-based manufacturing. https://www.nasa.gov/space-synthetic-biology-synbio/
[9] NASA Ames. Air Revitalization at ARC. https://www.nasa.gov/ames/space-biosciences/bioengineering-branch/air-revitalization-at-arc/• [10] Thermo Fisher Scientific. Phusion High-Fidelity PCR Master Mix with HF Buffer product and user guide. https://www.thermofisher.com/order/catalog/product/F531L
[11] Thermo Fisher Scientific. E-Gel EX Agarose Gels, 2%, with SYBR Gold II. https://www.thermofisher.com/order/catalog/product/G401002
[12] Thermo Fisher Scientific. E-Gel 1 Kb Plus Express DNA Ladder. https://www.thermofisher.com/order/catalog/product/10488091
[13] SecureDNA consortium. A system capable of verifiably and privately screening DNA synthesis orders. https://securedna.org/manuscripts/System_Screening_Global_DNA_Synthesis.pdf
[14] National Academies. Governance of Dual Use Research in the Life Sciences and related DNA synthesis screening discussion. https://www.nationalacademies.org/read/25154/chapter/5
[15] Benchling. PCR and Primer Design / primer design resources. https://help.benchling.com/hc/en-us/articles/9684234653837-PCR-and-Primer-Design
[16] Addgene. How to Design Primers. https://www.addgene.org/protocols/primer-design/
[17] Twist Bioscience. Digital DNA Data Storage overview. https://twistbioscience.com/products/storage