# Electronically Addressable DNA Assembly

> **NIH NIH R43** · AVERY BIO CORPORATION · 2023 · $275,766

## Abstract

The ability to routinely synthesize entire genomes is one of the great remaining technical aspirations of the
synthetic biology revolution. The complexity of designing the annealing reactions used by existing assembly
workflows is a fundamental barrier to genome-scale DNA production. There is a practical limit to the number of
distinct sequences which can reliably self-assemble into the desired construct in a single step, and traditional
assembly reactions are typically limited in scale to tens or hundreds of oligonucleotides. Current parallel
synthesis technologies can generate pools of over 1 million oligonucleotides, which is entirely inadequate for a
genome-scale construction, yet far more complex than can be reliably assembled in a single reaction. Despite
substantial interest in improving oligonucleotide synthesis throughput, such technologies cannot be leveraged
fully without accompanying means of guiding their assembly.
We have made advancements to generate oligonucleotides at a throughput 100× any published system. The
proposed studies work to translate this advance (up to 100× enhancement) to the throughput of gene assembly.
The underlying concept is to perform DNA synthesis on a substrate capable of controlling the localization of the
oligonucleotides during their subsequent assembly. If successful, the approach would address a fundamental
scalability mismatch between oligonucleotide synthesis and assembly, enabling a new generation of gene
synthesis technologies capable of exceeding the scale of the human genome with a single synthesis run. This
project may lead to a 100x parallelization increase and 100x cost decrease, and potentially increase assembly
accuracy.

## Key facts

- **NIH application ID:** 10697597
- **Project number:** 1R43GM150322-01
- **Recipient organization:** AVERY BIO CORPORATION
- **Principal Investigator:** Matthew Taylor Holden
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $275,766
- **Award type:** 1
- **Project period:** 2023-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10697597

## Citation

> US National Institutes of Health, RePORTER application 10697597, Electronically Addressable DNA Assembly (1R43GM150322-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10697597. Licensed CC0.

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