4/24 – Krishanu Saha, University of Wisconsin-Madison
Biomedical Engineering Seminar
April 24, 2026
11:00 AM - 12:00 PM
Location
BME Seminar in SEO 236
Address
851 S Morgan St, Chicago, IL 60607
Calendar
Download iCal FileSpeaker:
Krishanu Saha, PhD
Professor
Department of Biomedical Engineering
University of Wisconsin-Madison
Title: Towards Rapid, Automated Biomanufacturing of Cell and Gene Therapies with Nonviral Genome Editing
Abstract: Therapeutic genome editing holds significant promise for correcting harmful mutations and engineering novel cell functions using genetic circuits. However, turning these approaches into approved treatments is just starting, and many diseases still lack effective cures. Next-gen nonviral genome-editing tools could accelerate progress by enabling rapid customization and manufacturing of drug candidates without the need to produce new viral vector batches. In this presentation, I will discuss two efforts using synthetic nanoparticles—covering in vivo gene therapy and ex vivo cell therapy—that are in the preclinical stage and expected to begin first-in-human trials within 1-3 years.
The first effort is the CRISPR Vision Program, part of the US National Institutes of Health Somatic Cell Genome Editing Consortium (SCGE). Its goal is to develop nonviral genome editing platforms to treat inherited retinal channelopathies. For Leber Congenital Amaurosis (LCA16), a severe childhood blindness caused by mutations in the KCNJ13 gene, we are developing a novel gene therapy using a CRISPR adenine base editor (ABE8e) delivered via subretinal injection of nonviral lipid nanoparticles (LNPs). Our team carefully evaluates the safety and effectiveness of these formulations through various models. Encouraging results include successful correction of the W53X KCNJ13 mutation using LNP-based delivery of ABE8e mRNA, restoring Kir7.1 channel function. In vitro, precise gene correction confirmed by sequencing and functional improvement was shown in retinal pigment epithelial (RPE) cells derived from patient-induced pluripotent stem cells (iPSCs). We also demonstrate high accuracy and functional rescue with similar nanoparticles in Best disease models.
The second effort focuses on ex vivo edited immune cell therapies, utilizing new techniques for nonviral integration of large transgenes into human T and natural killer (NK) cells. The nonviral method, Cas9-CLIPT, involves nanometer-scale complexing of ribonucleoprotein complexes, facilitating precise and stable insertion of therapeutic genes up to 5 kb. This approach shows promise for improving autologous and allogeneic CAR T and NK cell therapies for cancer and autoimmune diseases. Our initial target for autologous T cell therapy is GD2+ solid tumors.
For both initiatives, we will share new insights from our interactions with the US FDA and discuss developing nonviral CRISPR platforms to address multiple genetic mutations and disease indications.
Date posted
Mar 13, 2026
Date updated
Apr 24, 2026