Biology subjects

Royzen, M.

Publications and source records attributed to Royzen, M..

2 recordsLinked to original sources

bioRxiv2020

SQ3370 Activates Cytotoxic Drug via Click Chemistry at Tumor and Elicits Sustained Responses in Injected & Non-injected Lesions

While systemic immuno-oncology therapies have shown remarkable success, only a limited subset of patients benefit from them. Our Click Activated Protodrugs Against Cancer (CAPAC) Platform is a click chemistry-based approach that activates cancer drugs at a specific tumor with minimal systemic toxicity. CAPAC Platform is agnostic to tumor characteristics that can vary across patients and hence applicable to several types of tumors. We describe the benefits of SQ3370 (lead candidate of CAPAC) to achieve systemic anti-tumor responses in mice bearing two tumors. SQ3370 consists of a biopolymer, injected in a single lesion, followed by systemic doses of an attenuated protodrug of doxorubicin (Dox). SQ3370 was well-tolerated at 5.9-times the maximum dose of conventional Dox, increased survival by 63% and induced a systemic antitumor response against injected and non-injected lesions. The sustained anti-tumor response also correlated with immune activation measured at both lesions. SQ3370 could potentially benefit patients with micro-metastatic lesions.

bioengineering↗

bioRxiv2020

Bio-Orthogonal Chemistry Enables Solid Phase Synthesis of Long RNA Oligonucleotides

Solid phase synthesis of RNA oligonucleotides which are over 100-nt in length remains to be challenging due to the complexity of purification of the target strands from the failure sequences. This work describes a non-chromatographic strategy that will enable routine solid phase synthesis of long RNA strands. The optimized five-step process is based on bio-orthogonal inverse electron demand Diels-Alder chemistry between trans-cyclooctene (TCO) and tetrazine (Tz) and entails solid phase synthesis of RNA on a photo-labile support. The target oligonucleotide strands are selectively tagged with Tz. After photocleavage from the solid support, the target oligonucleotide strands can be captured and purified from the failure sequences using immobilized TCO. The approach was optimized using a model 20-mer DNA strand and was successfully applied towards synthesis of 76-nt long tRNA and 101-nt long sgRNA. Purity of the isolated oligonucleotides was evaluated using gel electrophoresis and mass spectrometry, while functional fidelity of the sgRNA was confirmed using CRISPR-Cas9 experiments and flow cytometry.

biochemistry↗