results.md

idec-teams · Oct 8, 2024 · 26ce6d4 · 26ce6d4
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@@ -126,7 +126,7 @@ To this end, we propagated the SIAH1 SP phages in bacterial cells that contain a
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 ### What are the next steps?
-Once we confirm that the E3-dependent phage propagation system is working properly, we will gradually evolve SIAH1/2 with PACE from recognizing the native degron to recognizing the degron of the final target protein, NLRP3. This process, called a "substrate walk," will help us evolve the SIAH1/2 enzymes to specifically recognize and mark NLRP3 for degradation. If we are successful in finding a variant of SIAH1/2 that can target NLRP3, we will test its effects in living organisms to see if it can trigger the degradation of NLRP3 through a process called polyubiquitination. Importantly, we'll also test for any unwanted effects (off-target effects) of the SIAH1/2 variants and, if they occur, remove them in further rounds of evolution using the negative selection system introduced above. While we continue to fine-tune the selection system, we believe this method holds promise for developing new therapies using engineered enzymes as targeted protein degradation drugs.
+Once we confirm that the E3-dependent phage propagation system is working properly, we will gradually evolve SIAH1/2 with PACE from recognizing the native degron to recognizing the degron of the final target protein, NLRP3. This process, called a "substrate walk," will help us evolve the SIAH1/2 enzymes to specifically recognize and mark NLRP3 for degradation. If we are successful in finding a variant of SIAH1/2 that can target NLRP3, we will test its effects in mammalian cells to see if it can trigger the degradation of NLRP3 through a process called polyubiquitination. Importantly, we'll also test for any unwanted effects (off-target effects) of the SIAH1/2 variants and, if they occur, remove them in further rounds of evolution using the negative selection system introduced above. While we continue to fine-tune the selection system, we believe this method holds promise for developing new therapies using engineered enzymes as targeted protein degradation drugs.
 
 ## References