synthetic biology papers

In-situ Target Base Editing Combining with Biosensor-driven Strategy Reveals Critical Single Nucleotide Variants for Enhanced Recombinant Protein Secretion in Pichia pastoris

This study presents a novel BINDER strategy combining dual-base editor-mediated in-situ genome engineering with nanobody-regulated biosensor-driven droplet sorting to identify critical single nucleotide variants that significantly enhance recombinant human serum albumin secretion in *Pichia pastoris*, achieving a record-breaking titer of 23.43 g/L.

Tang, Y., Zhang, C.2026-04-10📄 synthetic biology

A bio-orthogonal and covalent 5 kDa small protein tag

This paper introduces CLUSTER, a novel bio-orthogonal platform combining SNAP-tag and intein-mediated splicing to enable efficient, minimally perturbative covalent labeling of proteins with a small 5 kDa fluorescent tag in living cells.

Pabst, U., Rossius, J., Olesen, C. H. + 2 more2026-04-10📄 synthetic biology

Multicenter preclinical validation of next-generation CAR T cells: a strategy for harmonization, reproducibility, and its feasibility in clinical translation

This study demonstrates the feasibility and success of a harmonized, multicenter preclinical validation strategy for next-generation CAR T cells, confirming that CCR8 overexpression enhances solid tumor infiltration without compromising cytotoxicity while establishing a reproducible framework to improve clinical translation.

Dalloul, I., Barden, M., Wilcke, J. + 5 more2026-04-10📄 synthetic biology

Existence and Localization of a Limit Cycle in a Class of Benchmark Biomolecular Oscillators

This paper establishes an elementary geometric proof for the existence of limit cycles in a class of biomolecular oscillators using the Brouwer Fixed Point theorem on a constructed toroidal manifold, while employing interval-based reachability analysis to rigorously localize these oscillatory solutions.

Mohanty, S., Sen, S.2026-04-10📄 synthetic biology

Systematic CRISPRi screening reveals genetic modulators of E. coli isoprenoid production

This study employs a systematic CRISPRi screening approach to identify 31 genetic modulators across diverse metabolic pathways in *E. coli* that significantly influence lycopene production, thereby revealing novel targets for rebalancing cellular metabolism to enhance isoprenoid yields.

Dokwal, D., Brown, P. M., Ingle, C. + 2 more2026-04-10📄 synthetic biology

Expression landscape of heterologous enzymes in Synechocystis sp. PCC 6803

This study systematically quantifies the degradation of 103 heterologous enzymes in *Synechocystis* sp. PCC 6803 using a novel split-GFP and CRISPRi approach, revealing that nearly half of these proteins are significantly degraded and demonstrating that swapping enzymes for homologs is often more effective than optimizing genetic elements for improving expression in cyanobacterial cell factories.

Medipally, H., Karlsson, A., Dheer, A. + 2 more2026-04-09📄 synthetic biology

Sequence Design and Phylogenetic Inference with Generative Flow Networks

This paper introduces AncestorGFN, a novel framework leveraging Generative Flow Networks to simultaneously perform alignment-free phylogenetic inference and sequence design by generating sequences whose flow trajectories implicitly encode evolutionary relationships and ancestral structures.

Huang, Q., Mourra-Diaz, C. M., Wen, X. + 1 more2026-04-09📄 synthetic biology

Maximally Divergent Synonymous Gene Design with SIRIUS

The paper introduces SIRIUS, a combinatorial optimization algorithm that uses integer linear programming to generate maximally divergent DNA sequences for a given protein while adhering to host-specific codon usage constraints, thereby outperforming existing heuristic and machine learning methods in minimizing shared subsequences to enhance synthetic strain stability.

Mohseni, A., Wheeldon, I., Lonardi, S.2026-04-07📄 synthetic biology

Exploring Chromosomal Position Effects for Predictable Tuning of Metabolic Pathways in Yeast

This study establishes a predictive framework, Yeast IGR Prophet, that leverages chromosomal position effects to rationally tune metabolic pathways in yeast by selecting optimal genomic integration sites, thereby achieving precise transcriptional stoichiometry without altering promoters or gene copy numbers.

Hong, H., Cai, Y., Wang, J. + 3 more2026-04-07📄 synthetic biology

Automated Knowledge Graph Construction for CAR T Cell Receptor Design via Hybrid Text Mining

This paper presents an automated workflow integrating NLP tools and large language models to construct a comprehensive knowledge graph of CAR T cell signaling interactions from PubMed literature, thereby providing a structured resource to guide the design of next-generation chimeric antigen receptors.

Luo, H., Tang, D., Zivanov, A. + 1 more2026-04-07📄 synthetic biology

End-to-end bimodal anti-counterfeiting by informational DNA nanoparticles

This paper presents InfinMark, a comprehensive end-to-end bimodal anti-counterfeiting framework that integrates IoT and DNA-of-Things technologies to utilize informational DNA nanoparticles for secure, scalable, and rapid product authentication from source labeling to terminal tracing.

He, T., Zhuo, B., Zhao, X. + 15 more2026-04-07📄 synthetic biology

DNA Protonuclei as Programmable Nuclear Mimics Reveal Environmental Context on Protein Phase Separation

This study introduces programmable DNA-based protonuclei as controllable nuclear mimics to demonstrate that environmental factors like spatial confinement and multivalent interactions critically regulate FUS protein phase separation and disease-related transitions, revealing limitations in traditional test-tube assays.

Dormann, D., Walther, A., Fritzen, J. + 3 more2026-04-07📄 synthetic biology

Gain-Scheduled Optogenetic Feedback for Disturbance Rejection in Bacterial Batch Cultures

This paper presents a multiscale model-guided control framework that employs gain-scheduled PID and feedback-feedforward strategies to achieve robust disturbance rejection in batch E. coli cultures by adapting to growth-phase-dependent dynamics that limit fixed-gain controllers.

Namboothiri, H. R., Hu, C. Y.2026-04-05📄 synthetic biology

Humanization of the rpb9 locus in fission yeast reveals conserved and divergent roles of rpb9 and human POLR2I

This study establishes an endogenous humanized fission yeast system to demonstrate that human POLR2I largely complements conserved and novel roles of yeast Rpb9 in growth, stress response, and heterochromatin assembly, while revealing specific context-dependent functional divergences in drug resistance.

Finkel, J. M., Williams, M. G., Nirmal, M. B. + 6 more2026-04-04📄 synthetic biology

Surface Display For Phage Assisted Continuous Evolution: A Platform For Evolving / Screening Nanobodies In Prokaryote Systems

This paper introduces SurPhACE, a scalable synthetic biology platform that combines *E. coli* surface display with {Phi}X174 phage-assisted continuous evolution to rapidly generate and screen high-affinity nanobodies in prokaryotic systems without the need for traditional library construction or animal inoculation.

Flores-Mora, F. E., Brodsky, J., Cerna, G. M. + 3 more2026-04-04📄 synthetic biology

Tuning a light-regulated allosteric switch for enhanced temporal control of protein activity

This study presents enhanced LightR variants with improved dynamic range and faster kinetics, enabling tunable, rapid, and reversible optogenetic control of Src kinase activity to better model diverse cellular signaling events.

Matsche, J., Fauser, J., Bansal, T. + 3 more2026-04-02📄 synthetic biology

Global Quantitative Analysis of Ligation Reactions in Self-Assembled DNA Nanostructures at the Single-Nick Level

This study employs quantitative PCR to globally analyze individual ligation reactions within DNA origami nanostructures, revealing that ligation efficiency is spatially dependent on ligase docking probability at edges versus inner sites, a trend that can be abolished by DMSO co-solvents, thereby providing critical insights for optimizing DNA nanostructure stability for real-world applications.

Hacker, K., Juricke, E., Munch, C. + 3 more2026-04-01📄 synthetic biology

Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells

This study introduces CRISPR-MACE, a continuous evolution platform that utilizes anti-CRISPR-mediated selection within human cells to successfully engineer novel Cas9 variants with enhanced DNA binding capabilities and significantly improved resistance to inhibitors, overcoming the limitations of traditional bacterial-based optimization.

Sabol, A. L., Mengiste, A. A., Singh, P. + 15 more2026-04-01📄 synthetic biology

Receptor-guided AAV Tropism Engineering via MATCH

The paper introduces MATCH, a modular biochemical platform that enables precise, receptor-guided retargeting of adeno-associated viruses (AAVs) via site-specific conjugation of homing proteins, thereby achieving efficient transduction of specific cell types like human T cells and enhanced brain delivery across the blood-brain barrier through a scalable, one-pot production strategy.

Graham, N., Kumar, S., Rainaldi, J. + 4 more2026-04-01📄 synthetic biology

Mathematical modeling and sensitivity analysis of synNotch-CAR T-cells identify engineering targets for dynamic tunability

This paper develops a multi-scale mathematical model and performs global sensitivity analysis on synNotch-CAR T-cells to identify key engineering targets, such as ligand association rates and promoter strength, that enable the dynamic tuning of therapeutic activity for cancer treatment.

Diefes, A. J., Sbaiti, B., Ciocanel, M.-V. + 1 more2026-04-01📄 synthetic biology