# GenSyn: A Cycle for Serial Assembly of Very Large DNA Molecules

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $265,465

## Abstract

Abstract
The broad, long-term objectives of the proposed research are development of a system for
direct, cell-free, validated fabrication of very large DNA assemblies, for applications in synthetic
applications and genome assembly. This system – “GenSyn” – will harness the advantages of
large DNAs for synthesis on supports in ways that will complement and synergize cell-based
techniques for the serial assembly of very large DNA molecules. The proposed research is
based on i) binding approaches supporting chemical and enzymatic processes; ii) shear-free
fluidic operations; iii) new methods for enhancing hybridization/ligation yields and iv) validations.
The devices are designed for gentle fluidic operations supporting assembly and image analysis
of large DNA constructs by epifluorescence microscopy. The first step in the GenSyn cycle will
be binding DNA molecules to a support by hybridization with oligonucleotides that are bound to
a derivatized glass surface. The hybridization and ligation steps will be optimized using physical
and chemical manipulations. Modified large DNAs will be used as coupler molecules, supporting
GenSyn cycles. Overall cycle performance metrics (coupling yields as a function of cycle
number, molecule breakage, reagent retention, timings and enzymatic activity) will be assessed
in ways that will inform and be guided by computer models. This research will help advance
fundamental studies on genomes and human health.

## Key facts

- **NIH application ID:** 10369379
- **Project number:** 1R21HG012281-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** DAVID C. SCHWARTZ
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $265,465
- **Award type:** 1
- **Project period:** 2022-01-19 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369379

## Citation

> US National Institutes of Health, RePORTER application 10369379, GenSyn: A Cycle for Serial Assembly of Very Large DNA Molecules (1R21HG012281-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10369379. Licensed CC0.

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