Biology subjects

Saltepe, B.

Publications and source records attributed to Saltepe, B..

3 recordsLinked to original sources

bioRxiv2025

Developing Anti-EGFR/Anti-HER2 Bifunctional Antibody for Solid Tumors by Protein Engineering

Overexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) is common in solid tumors like breast, colorectal, and head and neck cancers, driving oncogenic signaling, therapy resistance, and poor prognosis. Monotherapies often fall short in fully suppressing tumor progression, particularly in cases with EGFR/HER2 co-amplification. Dual-targeting strategies offer enhanced efficacy by mitigating resistance and amplifying antitumor responses. Our study focused on developing and characterizing a bispecific anti-EGFR/HER2 antibody designed to simultaneously block ligand binding and receptor activation while harnessing Fc-mediated immune effector functions. Utilizing knob-into-hole and CrossMab technologies, we engineered a bispecific antibody capable of binding the extracellular domains of both EGFR and HER2. In vitro analyses confirmed its dual-binding capacity. Comparative studies revealed that this bispecific construct outperformed its monospecific counterparts in suppressing proliferation and, notably, in increasing the expression of apoptotic markers in EGFR/HER2-expressing tumor cells. Together, these findings highlight the synergistic therapeutic potential of bispecific antibodies as a promising modality for overcoming the limitations of current monotherapies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/696462v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@192972corg.highwire.dtl.DTLVardef@102f9b2org.highwire.dtl.DTLVardef@57377corg.highwire.dtl.DTLVardef@1fbeb9d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Genetic Circuits Combined with Machine Learning Provides Fast Responding Living Sensors

Whole cell biosensors (WCBs) have become prominent in many fields from environmental analysis to biomedical diagnostics thanks to advanced genetic circuit design principles. Despite increasing demand on cost effective and easy-to-use assessment methods, a considerable amount of WCBs retains certain drawbacks such as long response time, low precision and accuracy. Furthermore, the output signal level does not correspond to a specific analyte concentration value but shows comparative quantification. Here, we utilized a neural network-based architecture to improve the aforementioned features of WCBs and engineered a gold sensing WCB which has a long response time (18 h). Two Long-Short Term-Memory (LSTM)-based networks were integrated to assess both ON/OFF and concentration dependent states of the sensor output, respectively. We demonstrated that binary (ON/OFF) network was able to distinguish between ON/OFF states as early as 30 min with 78% accuracy and over 98% in 3 h. Furthermore, when analyzed in analog manner, we demonstrated that network can classify the raw fluorescence data into pre-defined analyte concentration groups with high precision (82%) in 3 h. This approach can be applied to a wide range of WCBs and improve rapidness, simplicity and accuracy which are the main challenges in synthetic biology enabled biosensing.

synthetic biology↗

bioRxiv2018

Genetic Circuits to Detect Nanomaterial Triggered Toxicity through Engineered Heat Shock Response Mechanism

Biocompatibility assessment of nanomaterials has been of great interest due to their potential toxicity. However, conventional biocompatibility tests are short of providing a fast toxicity report. We developed a whole cell based biosensor to track biocompatibility of nanomaterials with the aim of providing fast feedback for engineering nanomaterials with lower toxicity levels. We have engineered promoters of four heat shock response proteins. As an initial design a reporter coding gene was cloned to downstream of the promoter regions selected. Initial results indicated that native HSP promoter regions were not very promising to generate signals with low background signals. Introducing riboregulators to native promoters eliminated unwanted background signal almost entirely. Unfortunately, this approach also leads a decrease in expected sensor signal. Thus, a repression based genetic circuit, inspired from HSP mechanism of Mycobacterium tuberculosis was constructed. These genetic circuits can report the toxicity of Quantum Dot nanoparticles in one hour with high precision. Our designed nanoparticle toxicity sensors can provide quick reports which can lower the demand for additional experiments with more complex organisms.

synthetic biology↗