Joseph Iwasyk

Nucleic acid therapeutics (NATs) offer transformative potential in targeting genetic diseases but face delivery challenges. Current methods like lipid nanoparticles and viral vectors optimize certain features but often compromise on others, limiting their overall efficacy. My thesis addresses these limitations by developing a hybrid system combining a cationic polymer (PEI) with nonviral protein cages (AaLS-13). This layered design improves nucleic acid encapsulation, stability, and endosomal… Meer weergeven

Nucleic acid therapeutics (NATs) offer transformative potential in targeting genetic diseases but face delivery challenges. Current methods like lipid nanoparticles and viral vectors optimize certain features but often compromise on others, limiting their overall efficacy. My thesis addresses these limitations by developing a hybrid system combining a cationic polymer (PEI) with nonviral protein cages (AaLS-13). This layered design improves nucleic acid encapsulation, stability, and endosomal escape. The electrostatically driven self-assembly process is simple and cost-effective. Assays confirmed capsid formation, stability, and protection of nucleic acids. This novel approach holds promise for more efficient, modular NAT delivery, potentially advancing therapeutic applications. Minder weergeven

Research Abstract: This project aimed to integrate proximity assays (PLA or PEA) with the portable peakPCR device to develop a sensitive, homogeneous point-of-care diagnostic for protein quantification. Traditional methods like Lateral Flow and RT-qPCR lack sensitivity or complexity, but proximity assays combine antibody targeting with PCR amplification for enhanced detection. A PLA protocol was modified to create a one-step assay with preloaded reagents in the peakPCR cartridge, enabling rapid… Meer weergeven

Research Abstract: This project aimed to integrate proximity assays (PLA or PEA) with the portable peakPCR device to develop a sensitive, homogeneous point-of-care diagnostic for protein quantification. Traditional methods like Lateral Flow and RT-qPCR lack sensitivity or complexity, but proximity assays combine antibody targeting with PCR amplification for enhanced detection. A PLA protocol was modified to create a one-step assay with preloaded reagents in the peakPCR cartridge, enabling rapid CRP detection. Further optimization focused on temperature, antibody concentration, and improving the signal-to-noise ratio. A custom proximity extension assay (PEA) was also developed, achieving an LOD of 0.17pM for CRP. Results demonstrated that proximity assays can be adapted for the peakPCR platform, offering rapid, sensitive detection of proteins in under 30 minutes. This approach shows potential for broader diagnostic applications, including detection of toxins, hormones, and other biomarkers.

Executive Summary for Innosuisse Application:
Antibiotics and drugs with a narrow therapeutic window require precision dosing to optimize patient outcomes. However, therapeutic-drug monitoring (TDM) is hindered by suboptimal dosing due to 1) non-standardized TDM assays and 2) limited data interpretation. These issues reduce therapeutic efficacy, increase toxicity, and contribute to antimicrobial resistance (AMR). Current TDM lacks integration with modeling software, preventing patient-specific dosing. Diaxxo is developing diaxxOmic, a personalized medicine platform using a low-cost, point-of-care qPCR device and single-use cartridge to rapidly quantify drugs, proteins, and nucleic acids. Data is sent to a pharmacology dashboard for real-time model-informed precision dosing (MIPD). The proof-of-concept "VancoPod" cartridge will monitor vancomycin pharmacokinetics (PK), pharmacodynamics (PD), and nephrotoxicity, aiming to reduce Acute Kidney Injury and optimize doses to combat AMR. Minder weergeven