2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
January 22nd, 2025
Version: 1
Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications
cancer biology
biorxiv

A bright synthetic near-infrared luciferin enhances the capabilities of deep-tissue bioluminescence imaging using firefly luciferases

Saito-Moriya, R.Open in Google Scholar•Iwano, S.Open in Google Scholar•Kitada, N.Open in Google Scholar•Yamasaki, N.Open in Google Scholar•Kamiya, G.Open in Google Scholar•Ogo, K.Open in Google Scholar•Sugiyama, T.Open in Google Scholar•Chuluun-Erdene, A.Open in Google Scholar•Isagawa, T.Open in Google Scholar•Obata, R.Open in Google Scholaret al.

Synthetic bioluminescence reactions exhibiting near-infrared (NIR)-shifted spectra have been explored to improve deep-tissue imaging through the design of firefly luciferin analogues. Although the NIR bioluminescence reactions improve the tissue penetration of bioluminescence signals from deep tissues, their photon output is markedly lower compared to the natural reaction with D-luciferin and firefly luciferase (Fluc), often by an order of magnitude or more. Consequently, in most instances, the sensitivity of NIR bioluminescence imaging (NIR-BLI) has not yet substantially surpassed that of BLI with the natural firefly reaction. Here, we present a synthetic firefly luciferin, named AkaSuke, that generates intense NIR bioluminescence ({lambda}max = 680 nm) in reaction with Fluc, greatly improving the detection sensitivity beyond that of the D-luciferin/Fluc reaction for targeting deep tissue. AkaSuke enables sensitive visualizations of ectopic hematogenesis through entire tissues of mice over time following transplantation of bone marrow stem cells labeled with Fluc. We additionally identify a Japanese firefly luciferase, DkumLuc1, that displays higher catalytic activities for bioluminescence emission of AkaSuke compared to typical Fluc, resulting in comparable detection sensitivity with the AkaLumine/Akaluc reaction, one of the most sensitive bioluminescence systems for deep tissue imaging. We further propose the potential of the AkaSuke/DkumLuc1 reaction as an orthogonal pair with the AkaLumine/Akaluc for sensitive dual-target tracking in mice. Overall results suggest that AkaSuke enhances the capabilities of deep-tissue bioluminescence imaging using Fluc and its variant, and could serve as an emerging benchmark for the molecular design of NIR luciferin analogues.

Similar Papers

biorxiv
Wed Jan 22 2025
PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP
Proteasome activator 28{gamma} (PA28{gamma}) plays a critical role in malignant progression of various tumors, however, its role and regulation are not well understood. Here, using oral squamous cell carcinoma (OSCC) as main research model, we discovered that PA28{gamma} interacted with complement 1q binding protein (C1QBP), which is dependent on the N-terminus of C1QBP rather than the known funct...
Wang, J.
•
Shi, Y.
•
Wang, Y.
•
Shen, Y.
...•
Chen, Q.
biorxiv
Wed Jan 22 2025
Genetically Defined Organoid Models Reveal Mechanisms Driving Squamous Cell Neoplastic Evolution and Identify Potential Therapeutic Vulnerabilities
Upper aerodigestive squamous cell carcinoma (UASCC) is an aggressive and lethal neoplasm, with its early neoplastic transformation mechanisms remaining poorly understood. Here, we characterize over 25 genetically-defined organoid models derived from murine and human oral/esophageal tissues harboring key driver mutations. Double knockout of TP53 and CDKN2A induced morphological dysplasia, hyperprol...
Zhao, H.
•
Park, Y. M.
•
Zheng, Y.
•
Mao, Q.
...•
Lin, D.-C.
biorxiv
Wed Jan 22 2025
Enhanced AkaLuc Bioluminescence Imaging for Longitudinal Intravital Monitoring of Minimal Residual Disease in a Murine Model of Triple-negative Breast Cancer
Triple-negative breast cancer (TNBC) is an aggressive form of cancer with poor prognosis. Beyond the absence of targeted therapies, a major challenge is its high recurrence rate, driven by the outgrowth of residual tumor cells that survive chemotherapy and persist during minimal residual disease (MRD). To monitor the therapy response of TNBC by enhanced intravital imaging, we established a clinica...
Steinbauer, S.
•
Cowles, J. D.
•
Sabbaghi, M. A.
•
Poppelaars, M.
...•
Csiszar, A.
biorxiv
Wed Jan 22 2025
When neighbours play a role: a systems-level analysis of protein interactions conditioning cancer driver mutation effects
Background: Cancer is driven by the accumulation of somatic mutations, including driver mutations that confer a selective advantage to cancer cells. Driver proteins operate within complex interaction networks, and their activity is conditioned by neighbour proteins. Understanding the interplay between driver mutations and the expression of their neighbour proteins can provide insights into cancer ...
Vital, M. F.
•
Miranda, J. A.
•
Carrolo, M.
•
Quintela, A.
•
Pinto, F. R.
biorxiv
Wed Jan 22 2025
Neoplastic immune mimicry is a generalizable phenomenon in breast cancer and epithelial CD69 enables early tumor progression
Dedifferentiation programs are commonly enacted during breast cancer progression to enable novel cellular phenotypes. Increased cellular plasticity within the neoplastic compartment of tumors correlates with disease aggressiveness, often culminating in greater resistance to cytotoxic therapies or the augmented ability to metastasize to distant organs. Here we report that subpopulations of dediffer...
Berens, E. B.
•
Khou, S.
•
Huang, E.
•
Hoffman, A.
...•
Coussens, L. M.
biorxiv
Wed Jan 22 2025
RAS-PI3K Pathway in CAFs Shapes Physicochemical Properties of Tumor ECM and restrains Tumor progression
Cancer-associated fibroblasts (CAFs) are key regulators of the tumor microenvironment, promoting tumor progression through extracellular matrix (ECM) remodeling and paracrine signaling, but the signaling pathways controlling CAF function remain incompletely defined. Here, we demonstrate that RAS-PI3K signaling plays a central role in CAF activation and ECM remodeling by promoting collagen crosslin...
Cuesta, C.
•
Alcon-Perez, M.
•
Zheng, J.
•
Procel, N.
...•
Castellano, E.
biorxiv
Wed Jan 22 2025
PI3K regulates TAZ/YAP and mTORC1 axes that can be synergistically targeted
Purpose: Sarcomas are a heterogeneous group of cancers with few shared therapeutic targets. PI3K signaling is activated in various subsets of sarcomas, representing a shared oncogenic signaling pathway. Oncogenic PI3K signaling has been challenging to target therapeutically. An integrated view of PI3K and Hippo pathway signaling is examined to determine if this could be leveraged therapeutically. ...
Garcia, K. C.
•
Khan, A. A.
•
Ghosh, K.
•
Sinha, S.
...•
Tanas, M. R.
biorxiv
Wed Jan 22 2025
Potent synthetic lethality between PLK1 and EYA-family inhibitors in tumours of the central and peripheral nervous system
The Eyes Absent family of protein phosphatases (EYA1-4) are aberrantly expressed and tumour-promoting across many devastating cancers of neurological origin affecting both children and adults. It has recently been demonstrated that EYA1 and EYA4 promote tumour cell survival by increasing the active pool of Polo-like kinase 1 (PLK1) molecules. This discovery provides a rationale for the therapeutic...
Nelson, C. B.
•
Wells, J. K.
•
Kesarwani, E.
•
Sobinoff, A. P.
...•
Pickett, H. A.
biorxiv
Wed Jan 22 2025
araCNA: Somatic copy number profiling using long-range sequence models
Somatic copy number alterations (CNAs) are hallmarks of cancer. Current algorithms that call CNAs from whole genome sequenced (WGS) data have not exploited deep learning methods owing to computational scaling limitations. Here, we present a novel deep-learning approach, araCNA, trained only on simulated data that can accurately predict CNAs in real WGS cancer genomes. araCNA uses novel transformer...
Visscher, E.
•
Yau, C.