From 26ce6d4f164db557e003a9929b84b6ffa6fff6e9 Mon Sep 17 00:00:00 2001 From: Max <63072723+X-E-M-E-X@users.noreply.github.com> Date: Wed, 9 Oct 2024 00:12:02 +0200 Subject: [PATCH] results.md --- docs/project/results.md | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/docs/project/results.md b/docs/project/results.md index 94758c2..363281e 100644 --- a/docs/project/results.md +++ b/docs/project/results.md @@ -126,7 +126,7 @@ To this end, we propagated the SIAH1 SP phages in bacterial cells that contain a ### 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