{"id":"CU24283","slug":"combinatorial-protein-design--CU24283","source":{"id":"CU24283","dataset":"techtransfer","title":"Combinatorial protein design platform for safe, high-potency CRISPR activators","description_":"<p>This technology is a combinatorial protein design platform that rapidly generates and screens engineered protein variants to produce safer, more potent CRISPR gene activators for research, biotechnology, and therapeutic applications.</p>\r\r<h2>Unmet Need: Scalable platform for low-toxicity, high-performance CRISPR activators</h2>\r\r<p>Current CRISPR gene activation systems can exhibit inconsistent effectiveness across different genes and cell types, unintended activation of non-target genes, and cellular toxicity, limiting safe use. Efforts to improve these tools are hindered by slow, low-throughput development methods that make it difficult to systematically optimize performance while minimizing harmful effects. These challenges reduce research reliability and pose barriers to clinical translation. </p>\r\r<h2>The Technology: Rapid barcoded screening of engineered CRISPR activator variants</h2>\r\r<p>The technology uses a combinatorial protein engineering approach to generate large libraries of engineered protein variants by assembling different functional domains into new configurations, each labeled with a unique barcode that enables simultaneous pooled testing of thousands of designs in cells. Gene activation performance and cellular fitness are measured in parallel, allowing potent variants to be identified while toxic designs are naturally depleted. Because full-length domains or entire proteins can be combined, the platform can explore a wide range of designs directly in living cells.</p>\r\r<p>This technology was validated by the identification of two engineered CRISPR activators (MHV and MMH) that demonstrate strong gene activation across multiple targets and cell types while exhibiting lower cellular toxicity than commonly used activators.</p>\r\r<h2>Applications:</h2>\r\r<ul>\r<li>Potent, low-toxicity CRISPR activators for robust gene activation across targets and cell types</li>\r<li>Platform for large-scale discovery and optimization of engineered protein variants </li>\r<li>Engineering of immune cells and stem cells for therapeutic applications </li>\r<li>Synthetic biology and programmable genetic circuit development </li>\r<li>Clinical gene therapy </li>\r</ul>\r\r<h2>Advantages:</h2>\r\r<ul>\r<li>High-throughput generation and screening of protein variants </li>\r<li>Faster discovery</li>\r<li>Generalizable to diverse proteins and applications </li>\r<li>Lower cellular toxicity</li>\r<li>Strong, consistent gene activation across targets and cell types</li>\r</ul>\r\r<h2>Lead Inventor:</h2>\r\r<p><a href=\"https://systemsbiology.columbia.edu/faculty/alejandro-chavez\">Alejandro Chavez, Ph.D.</a></p>\r\r<h2>Patent Information:</h2>\r\r<p>Patent Pending</p>\r\r<h2>Related Publications:</h2>\r\r<ul>\r<li><a href=\"https://www.nature.com/articles/s41467-025-65986-4\">Giddins M, Kratz AF, De Los Santos MB, et al. “Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.” Nat Commun. 2025;16:11114.</a></li>\r</ul>\r\r<h2>Tech Ventures Reference:</h2>\r\r<ul>\r<li><p>IR CU24283 </p></li>\r<li><p>Licensing Contact: <a href=\"mailto:techtransfer@columbia.edu\">Cynthia Lang</a></p></li>\r</ul>\r","tags":["CRISPR","Combinatorics","DNA barcoding","Gene therapy","High-throughput screening","Protein","Protein engineering","Synthetic biology"],"file_number":"CU24283","collections":[],"meta_description":"A high-throughput combinatorial protein design platform identifies potent, low-toxicity CRISPR activators across targets and cell types.","apriori_judge_output":"{\"scores\":{\"novelty\":4.0,\"potential_impact\":4.0,\"readiness\":3.0,\"scalability\":4.0,\"timeliness\":3.0},\"weighted_score\":3.4,\"risks\":[\"Moderate regulatory/clinical translation risk due to CRISPR-based activators\",\"Competition and IP landscape uncertainty\",\"Need for in vivo safety validation and off-target assessment\"],\"one_sentence_take\":\"High novelty and potential impact with scalable design platform, but readiness and timeliness are moderated by translational and regulatory hurdles.\"}","inventors":["Alejandro Chavez","Marla Giddins"],"manager":"Cynthia Lang","depts":["Microbiology","Pathology & Cell Biology"],"divs":["Columbia University Medical Center (CUMC)"],"date_released":"2026-04-10"},"highlight":{},"matched_queries":null,"score":0.0}