{"id":"CU21170","slug":"simultaneous-gene-silencing--CU21170","source":{"id":"CU21170","dataset":"techtransfer","title":"Simultaneous gene silencing and augmentation for restoration of BEST1-associated retinal degeneration","description_":"<p>This technology is a combination of CRISPR/dCas9-mediated gene silencing and baculovirus-delivered gene augmentation to restore the healthy function of bestrophin-1 (BEST1) for the treatment of bestrophinopathies. </p>\r\r<h2>Unmet Need: Mutation-agnostic, therapies for BEST1-associated retinal degeneration</h2>\r\r<p>Mutations in the bestrophin-1 (BEST1) gene, which encodes a calcium activated channel, can result in a spectrum of retinal degenerative disorders collectively known as bestrophinopathies. Over 250 disease-causing BEST1 mutations have been identified, yet there are currently no available treatments. For loss-of-function mutations, introducing a functional copy of the gene is a feasible approach. However, traditional gene augmentation alone cannot overcome the strong dominant effects of gain-of-function mutations. Therefore, there remains a significant unmet need for a customizable method to manipulate BEST1 expression that caters to the specific genetic profile of individual patients.</p>\r\r<h2>The Technology: Customizable CRISPR/dCas9 gene silencing paired with gene augmentation to restore BEST1 function</h2>\r\r<p>This technology is a customizable method of combining gene augmentation with gene silencing to restore healthy function of BEST1. This targeted strategy effectively restores calcium-dependent chloride channel activity, providing a universal treatment option for both loss-of-function and gain-of-function BEST1 mutations.</p>\r\r<p>This technology has been validated in HEK293 cells and human pluripotent stem cells.</p>\r\r<h2>Applications:</h2>\r\r<ul>\r<li>Gene therapy for retinal degeneration</li>\r<li>Genetic models for retinal disease research </li>\r<li>Restoration of function for patients with loss-of-function and gain-of-function BEST1 mutations</li>\r<li>Research tool for characterizing ion channels in the retinal pigmented epithelium</li>\r</ul>\r\r<h2>Advantages:</h2>\r\r<ul>\r<li>Universal treatment strategy</li>\r<li>Targets loss-of-function and gain-of-function mutations</li>\r<li>Precise suppression</li>\r<li>Patient-specific and highly customizable</li>\r</ul>\r\r<h2>Lead Inventor:</h2>\r\r<p><a href=\"https://www.pathology.columbia.edu/profile/stephen-h-tsang-md\">Stephen H. Tsang, MD, Ph.D.</a></p>\r\r<h2>Patent Information:</h2>\r\r<p>Patent Pending(<a href=\"https://patents.google.com/patent/US20240043848A1/en?oq=WO/2022/221411\">US20240043848</a>)</p>\r\r<h2>Related Publications:</h2>\r\r<ul>\r<li><p><a href=\"https://pubmed.ncbi.nlm.nih.gov/34061021/\">Zhao Q, Kong Y, Kittredge A, Li Y, Shen Y, Zhang Y, Tsang SH, Yang T. Distinct expression requirements and rescue strategies for BEST1 loss- and gain-of-function mutations. Elife. 2021 Jun 1;10:e67622.</a></p></li>\r<li><p><a href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910965/\">Ji C, Li Y, Kittredge A, Hopiavuori A, Ward N, Yao P, Fukuda Y, Zhang Y, Tsang SH, Yang T. Investigation and Restoration of BEST1 Activity in Patient-derived RPEs with Dominant Mutations. Sci Rep. 2019 Dec 13;9(1):19026.</a></p></li>\r</ul>\r\r<h2>Tech Ventures Reference:</h2>\r\r<ul>\r<li><p>IR CU21170</p></li>\r<li><p>Licensing Contact: <a href=\"mailto:kn2557@ctv.columbia.edu\">Kristin Neuman</a> </p></li>\r</ul>\r","tags":["CRISPR","Calcium channel","Chloride channel","Gene therapy","HEK 293 cells","Induced pluripotent stem cell","Ion","Mutation","Retina","Retinal pigment epithelium","Retinopathy"],"file_number":"CU21170","collections":[],"meta_description":"Mutation-agnostic CRISPR/dCas9 silencing plus gene augmentation restores BEST1 channel function in retinal cells.","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":2.0,\"scalability\":3.0,\"timeliness\":2.0},\"weighted_score\":2.9,\"risks\":[\"Preclinical (in vitro) validation only; in vivo delivery and safety unproven\",\"Delivery method (baculovirus) viability and regulatory risk for ocular gene therapy\",\"Potential immunogenicity and off-target effects of CRISPR/dCas9 approach\",\"Scalability of manufacturing for patient-specific customization not yet demonstrated\",\"Patent/pipeline and regulatory pathway unclear; reliance on platform with multiple mutation profiles\"],\"one_sentence_take\":\"Promising novel dual CRISPR/dCas9 silencing plus gene augmentation approach with broad applicability, but preclinical and delivery/regulatory hurdles limit readiness and risk-adjusted scalability.\"}","inventors":["Stephen H. Tsang M.D., Ph.D.","Tingting Yang","Yu Zhang"],"manager":"Joan Martinez","depts":["Ophthalmology"],"divs":["College of Physicians and Surgeons (CUMC","Columbia University Medical Center (CUMC)"],"date_released":"2026-06-05"},"highlight":{},"matched_queries":null,"score":0.0}