Exploring the potential of water channels for developing genetically encoded reporters and biosensors for diffusion-weighted MRI DOI Creative Commons

Asish N. Chacko,

Austin D.C. Miller,

Kaamini M. Dhanabalan

et al.

Journal of Magnetic Resonance, Journal Year: 2024, Volume and Issue: 365, P. 107743 - 107743

Published: July 18, 2024

Genetically encoded reporters for magnetic resonance imaging (MRI) offer a valuable technology making molecular-scale measurements of biological processes within living organisms with high anatomical resolution and whole-organ coverage without relying on ionizing radiation. However, most MRI rely synthetic contrast agents, typically paramagnetic metals metal complexes, which often need to be supplemented exogenously create optimal contrast. To eliminate the we previously introduced aquaporin-1, mammalian water channel, as new reporter gene fully autonomous detection genetically labeled cells using diffusion-weighted MRI. In this study, aimed expand toolbox diffusion-based genetic by modulating aquaporin membrane trafficking harnessing evolutionary diversity channels across species. We identified number that functioned genes. addition, show loss-of-function variants yeast human aquaporins can leveraged design first-in-class sensors detecting activity model protease cells.

Language: Английский

Exploring the potential of water channels for developing MRI reporters and sensors without the need for exogenous contrast agents DOI Creative Commons

Asish N. Chacko,

Austin D.C. Miller,

Kaamini M. Dhanabalan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 23, 2024

Abstract Genetically encoded reporters for magnetic resonance imaging (MRI) offer a valuable technology making molecular-scale measurements of biological processes within living organisms with high anatomical resolution and whole-organ coverage without relying on ionizing radiation. However, most MRI rely contrast agents, typically paramagnetic metals metal complexes, which often need to be supplemented exogenously create optimal contrast. To eliminate the we previously introduced aquaporin-1, mammalian water channel, as new reporter gene fully autonomous detection genetically labeled cells using diffusion-weighted MRI. In this study, aimed expand toolbox diffusion-based genetic by modulating aquaporin membrane trafficking harnessing evolutionary diversity channels across species. We identified number that functioned genes. addition, show loss-of-function variants yeast human aquaporins can leveraged design first-in-class sensors detecting activity model protease cells.

Language: Английский

Citations

1
A dual-gene reporter-amplifier architecture for enhancing the sensitivity of molecular MRI by water exchange DOI Creative Commons
Yimeng Huang, Xinyue Chen, Ziyue Zhu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 25, 2024

Abstract The development of genetic reporters for magnetic resonance imaging (MRI) is essential investigating biological functions in intact animals. However, current MRI have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small percentage cells express reporter. To overcome this limitation, we developed an approach that amplifies signals by co-expressing reporter gene, Oatp1b3, with water channel, aquaporin-1 (Aqp1). We first show expression Aqp1 paramagnetic relaxation effect Oatp1b3 facilitating transmembrane exchange. This mechanism provides Oatp1b3-expressing access larger pool compared typical exchange-limited conditions. further demonstrated our methodology allows dual-labeled be detected using approximately 10-fold lower concentrations agent than Aqp1-free scenario. Finally, enables mixed-cell populations containing fraction Oatp1b3-labeled are otherwise undetectable based on alone.

Language: Английский

Citations

0
A Dual‐Gene Reporter‐Amplifier Architecture for Enhancing the Sensitivity of Molecular MRI by Water Exchange DOI
Yimeng Huang, Xinyue Chen, Ziyue Zhu

et al.

ChemBioChem, Journal Year: 2024, Volume and Issue: 25(10)

Published: March 5, 2024

The development of genetic reporters for magnetic resonance imaging (MRI) is essential investigating biological functions in vivo. However, current MRI have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction cells express reporter. To overcome this limitation, we developed an approach amplifying sensitivity molecular by combining chemogenetic mechanism with biophysical increase water diffusion through co-expression dual-gene construct comprising organic anion transporting polypeptide, Oatp1b3, and channel, Aqp1. We first show that expression Aqp1 amplifies cultured engineered Oatp1b3. demonstrate amplification caused Aqp1-driven exchange, which provides gadolinium ions internalized Oatp1b3-expressing access larger pool compared exchange-limited conditions. further our methodology allows be detected using approximately 10-fold lower concentrations than Aqp1-free scenario. Finally, enables mixed-cell cultures containing Oatp1b3-labeled are undetectable on basis Oatp1b3 alone.

Language: Английский

Citations

0
Exploring the potential of water channels for developing genetically encoded reporters and biosensors for diffusion-weighted MRI DOI Creative Commons

Asish N. Chacko,

Austin D.C. Miller,

Kaamini M. Dhanabalan

et al.

Journal of Magnetic Resonance, Journal Year: 2024, Volume and Issue: 365, P. 107743 - 107743

Published: July 18, 2024

Genetically encoded reporters for magnetic resonance imaging (MRI) offer a valuable technology making molecular-scale measurements of biological processes within living organisms with high anatomical resolution and whole-organ coverage without relying on ionizing radiation. However, most MRI rely synthetic contrast agents, typically paramagnetic metals metal complexes, which often need to be supplemented exogenously create optimal contrast. To eliminate the we previously introduced aquaporin-1, mammalian water channel, as new reporter gene fully autonomous detection genetically labeled cells using diffusion-weighted MRI. In this study, aimed expand toolbox diffusion-based genetic by modulating aquaporin membrane trafficking harnessing evolutionary diversity channels across species. We identified number that functioned genes. addition, show loss-of-function variants yeast human aquaporins can leveraged design first-in-class sensors detecting activity model protease cells.

Language: Английский

Citations

0