Kinsey, A. | Search bioRxiv

bioRxiv2026

An Improved Manufacturing Method for Infusible Extracellular Matrix Materials to Enable Efficient Scale-Up, Improved Efficacy, and Clinical Translation

Decellularized extracellular matrix (ECM) materials are a popular choice for tissue engineering and regenerative medicine applications due to their multifaceted bioactive capabilities arising from their heterogenous composition. For minimally invasive delivery, infusible ECM (iECM) was developed through fractionation of digested decellularized ECM, allowing the material to be safely delivered intravascularly. iECM localizes to permeable vasculature in inflamed tissues and exerts immunomodulatory and pro-reparative effects with proof-of-concept already demonstrated in multiple preclinical models including myocardial infarction (MI) and multiple organ dysfunction syndrome (MODS). However, one major limitation of iECM is the steps required for manufacturing, involving centrifugation, dialysis/lyophilization, and filtration (C-D-F). These steps limit manufacturing output and iECM concentration, and require significant human handling, limiting compliance with current good manufacturing practices (cGMP). To overcome these challenges, we developed a method for manufacturing iECM that utilizes depth filtration and tangential flow filtration (DF-TFF), which reduces manufacturing time, allows for increased iECM concentration, and reduces human manipulation of material, improving translatability and scalability of iECM materials. Based on multiple material characterization methods, we determined that iECM made with DF-TFF was comparable to iECM made with C-D-F. By increasing iECM concentration through this manufacturing method, we demonstrate a dose dependent response in an acute MI porcine model and a mouse MODS model. Finally, DF-TFF enabled timely production of iECM from alternative tissue sources. Altogether, DF-TFF allows for improvements in production time, scale-up, cGMP compliance, and increased dose through higher concentration, paving the way for future clinical translation as well new preclinical studies.

bioengineering↗

bioRxiv2026

Integrated single-cell profiling of RNA and DNA interactomes reveals targetable chromatin architectures in cancer

The human genome is pervasively transcribed into protein-coding and regulatory non-coding RNAs whose functions are coordinated within higher-order nuclear architectures. However, direct mapping of RNA-RNA and DNA-DNA interaction networks in complex human tissues at single-cell resolution has remained a major challenge. Here, we present SCIENCE-seq, a multimodal single-cell interactomics platform enabling simultaneous detection of RNA-RNA interactions and chromatin DNA-DNA contacts within individual cells. Applied to primary glioma specimens, SCIENCE-seq reveals cancer-specific interactions organized by lncRNAs and centered on key oncogenic drivers, including EGFR, hTERT, SOX2, CDK6, CDC42, CD47, and HOX loci. These datasets uncover previously unrecognized molecular relationships between premature lncRNAs and pre-mRNAs that regulate transcription, alternative splicing, and polyadenylation. Notably, we identify a glioma-specific trans-chromosomal HOX hub driven by five interacting lncRNAs. Targeting specific RNA and DNA interactions using steric antisense oligonucleotides (ASOs) or CRISPRi selectively suppresses oncogenic programs in malignant cells while sparing normal tissue, establishing chromatin interactomes as actionable therapeutic targets.

cancer biology↗