Degradation

Chimeric antigen receptor natural killer (CAR-NK) cells represent a promising "off-the-shelf" alternative to CAR-T cells.

This review examines recent advancements in nanoparticle( s) (NPs) delivery systems, with a focus on ... lipid nanoparticles (LNPs)... We discussed various NP platforms and their applications, such as ... dry powder formulations of mRNA-loaded LNPs for pulmonary delivery, and LNP-mediated siRNA delivery for respiratory infections.

Cry2 is a blue-light photoreceptor cryptochrome from Arabidopsis used as a light-responsive multi-component optogenetic switch. The supplied evidence supports blue-light-dependent photoactivation linked to regulation of transcription factor control and to CRY2 degradation.

Prime editing is mentioned in the cited review as part of the broader set of genome-editing approaches considered in bacterial genome engineering. The supplied evidence does not describe its molecular architecture, target scope, or editing outcomes.

Here, we developed a genetically encoded biosensor, cdiGEBS, based on the transcriptional activity of the c-di-GMP-responsive transcription factor MrkH.

The CRY2-lacZ gene fusion is a Saccharomyces cerevisiae reporter construct used to measure how CRY2 sequence features regulate reporter expression. It was applied to identify cis-acting elements involved in repression of CRY2, linking CRY2-derived nucleotide information to lacZ output.

The development of KEAP1-recruiting PROTACs utilizing ligands derived from different classes of known KEAP1 inhibitors-including short peptides, covalent small molecules (e.g., CDDO derivatives), and non-covalent inhibitors (e.g., KI696)-is discussed.

First, we developed a constitutive excitatory synapse ablator, PFE3, analogous to the inhibitory synapse ablator GFE3. PFE3 targets the RING domain of the E3 ligase Mdm2 and the proteasome-interacting region of Protocadherin 10 to the scaffolding protein PSD-95, leading to efficient ablation of excitatory synapses.

Here, we consider the potential of macrocyclic peptides to overcome this limitation.

Between 2020 and 2025, major progress has been achieved across five modalities: ... autophagy-targeting chimeras (AUTACs) and related tethering strategies...

Bacterial degraders are a proposed construct pattern for targeted protein degradation in bacteria. They are discussed as tools to interrogate protein function and as potential antimicrobial modalities.

Bacterial degrons are proteolysis-targeting signals that are appended to proteins to direct their degradation in bacterial cells. They are described as tools to interrogate and control protein function through targeted protein depletion.

MCs are embedded in the final product and therefore need to be edible... the third scenario appears to be the most promising one for a production process. Indeed, using an edible material can limit or completely eliminate dissociation/degradation/separation steps and even promote organoleptic qualities when embedded in the final product.

Between 2020 and 2025, major progress has been achieved across five modalities: ... lysosome-targeting chimeras (LYTACs)... Each exploits endogenous degradation or regulatory pathways using chemically engineered bifunctional or monofunctional small molecules.

Between 2020 and 2025, major progress has been achieved across five modalities: proteolysis-targeting chimeras (PROTACs), molecular glues... Each exploits endogenous degradation or regulatory pathways using chemically engineered bifunctional or monofunctional small molecules.

Orthogonal degrons are bacterial construct patterns used in tunable degradation systems to direct targeted proteolysis of proteins of interest. The cited literature places them among recent advances that enable large screens and functional interrogation through regulated protein degradation.

PROteolysis TArgeting Chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands; an "anchor" to bind to an E3 ubiquitin ligase and a "warhead" to bind to a protein of interest, connected by a chemical linker.

The development of proteolysis targeting chimeras (PROTACs) that trigger degradation of the target proteins provides a conceptually novel approach to address drug targets that remained previously elusive.

Between 2020 and 2025, major progress has been achieved across five modalities: ... and ribonuclease-targeting chimeras (RIBOTACs). Each exploits endogenous degradation or regulatory pathways using chemically engineered bifunctional or monofunctional small molecules, thereby expanding the druggable proteome and transcriptome.

These heterobifunctional molecules are comprised of three units: a ligand for the protein of interest (POI), a ligand for an E3 ubiquitin ligase, and a linker that tethers the two motifs together. Von Hippel-Lindau (VHL) is one of the most widely employed E3 ligases in PROTACs development.

In the present study, transgenic tobacco lines with constitutive SsDHN expression (SsDHN-OE) were employed to examine its influence on seedling development under water-limited conditions.

CRY2-GFP is a C-terminal green fluorescent protein fusion of Arabidopsis cryptochrome 2 used to probe CRY2 blue-light responses. In the cited Plant Cell study, this fusion displayed constitutive biochemical and physiological activity and underwent blue-light-induced degradation more slowly than GFP-CRY2 or endogenous CRY2.

GFP-CRY2 is an N-terminal green fluorescent protein fusion to Arabidopsis CRY2. In the cited Plant Cell study, this fusion retained blue light-dependent biochemical and physiological activities similar to endogenous CRY2 and showed blue light-responsive degradation behavior more similar to native CRY2 than the reciprocal CRY2-GFP construct.

Jalpha helix point mutations disrupting LOV-domain interaction are a phototropin construct pattern in which residues along the Jα helix are mutated to weaken LOV–Jα intramolecular association. In full-length phototropin, these mutations displace or unfold the Jα helix and produce constitutive kinase activation in the absence of illumination.

Here, we constructed lysosome-localized optogenetic actuators, named lyso-NpHR3.0, lyso-ArchT, and lyso-ChR2, to achieve optogenetic manipulation of lysosomes.

Here, we constructed lysosome-localized optogenetic actuators, named lyso-NpHR3.0, lyso-ArchT, and lyso-ChR2, to achieve optogenetic manipulation of lysosomes. Notably, lyso-ChR2 activation induces autophagy through the mTOR pathway, promotes Aβ clearance in an autophagy-dependent manner in cellular models, and alleviates Aβ-induced paralysis in the Caenorhabditis elegans model of Alzheimer's disease.

Here, we constructed lysosome-localized optogenetic actuators, named lyso-NpHR3.0, lyso-ArchT, and lyso-ChR2, to achieve optogenetic manipulation of lysosomes.

opto-PROTAC is a light-inducible PROTAC design in which a photolabile caging group is installed on pomalidomide-based degraders to block activity in the dark and permit target protein degradation after ultraviolet A irradiation. It was demonstrated using caged pomalidomide and the PROTACs dBET1 and dALK to achieve spatiotemporal control of protein destruction.

In addition, we developed a light-inducible version of GFE3, paGFE3, using a novel photoactivatable complex based on the photocleavable protein PhoCl2c. paGFE3 degrades Gephyrin and ablates inhibitory synapses in response to 400 nm light.

pc-PROTAC1 is a photocaged PROTAC construct designed for light-dependent targeted protein degradation in live cells. In the cited study, it exhibited potent degradation activity only after light irradiation, establishing a light-activated degradation strategy.

Photo-caged PROTACs (pc-PROTACs) are light-activated proteolysis-targeting chimeras designed to trigger targeted protein degradation only after irradiation. The reported study presented pc-PROTACs as a general strategy for inducing degradation activity with light and showed that pc-PROTAC1 was potently active in live cells only after light exposure.

Split-Cas9-based targeted gene editing is a gene-editing component used in an optogenetically coordinated platform with nanobody-mediated proteolysis-targeting chimeras. In the reported application, it was used to regulate Survivin as part of a multi-level strategy to control cancer cell fate.

TRIM21-nanobody chimeras are engineered Trim-Away constructs that fuse TRIM21 activity to nanobody-based target recognition. In the cited 2020 work, these chimeras were described as highly active and were further adapted for optogenetic control of targeted protein degradation.

Auxin signalling is mediated, at least in large part, by an SCFTIR1 E3 ubiquitin ligase complex that accelerates Aux/IAA repressor degradation in response to IAA, thereby altering gene expression.

Finally, we developed a chemically inducible version of GFE3, chGFE3, which degrades inhibitory synapses when combined with the bio-orthogonal dimerizer HaloTag ligand-trimethoprim.

The PCB synthesis expression vector is a mammalian multigene construct that coexpresses heme oxygenase 1, phycocyanobilin:ferredoxin oxidoreductase, ferredoxin, and ferredoxin-NADP+ reductase to drive phycocyanobilin synthesis in mitochondria. It is used to supply the chromophore required for PhyB-PIF optogenetic systems without external PCB supplementation.

The CRY2 and LOV-fused degron light-responsive repression/degradation system is a multi-component optogenetic platform reported in mammalian cells that uses light to simultaneously block transcription and deplete protein levels. It is based on Arabidopsis cryptochrome 2 (CRY2), which interacts with CIB1 upon illumination, together with a LOV-fused degron configuration.

Flash-Away is an intrabody-directed optogenetic protein degradation system that enables blue-light-triggered, targeted degradation of selected proteins. It has been reported to act on actin, MLKL, and ALFA-tagged proteins.

This analysis identifies OsTIR1-based AID 2.0 as the most robust system. However, AID 2.0's higher degradation efficiency comes with target-specific basal degradation and slower recovery rates.

The resulting degron system, named AID 2.1, maintains effective target protein depletion with minimal basal degradation and faster recovery after ligand washout, enabling characterization and rescue experiments for essential genes.

Deg-LITer is a multi-component optogenetic gene circuit in which the TetR repressor is fused to a degradation tag through the LOV2 light-sensitive domain. It is part of the LITer toolset for light-controlled regulation in mammalian cells.

Hybrid nanocarriers have emerged as a transformative development in modern precision oncology, enabling the co-delivery of gene therapy and immunotherapy agents in a highly targeted manner.

Light-Inducible Tuner (LITer) is a mammalian optogenetic gene-circuit platform in which TetR is fused through the LOV2 light-sensitive domain to either a Tet-inhibitory peptide or a degradation tag. It enables light-controlled negative-feedback regulation of gene expression and was reported to reduce expression noise while providing tunable output control.

This Logic-gated AdPROM deploying SrtA-mediated Element Recombination (LASER) platform allows us to expand the possible protein degradation outcomes in mammalian cells using Boolean logic operations depending on the input combinations.

Lysosome-targeting chimeras (LYTACs), utilizing the endocytosis-lysosomal route, facilitate the selective degradation of secreted and transmembrane proteins.

Several types of synthetic receptors have been engineered to deliver specific therapeutic proteins, including ... modular extracellular sensor architecture (MESA)...

The supplied summary states that the review includes adjacent degrader modalities such as molecular glues and situates PROTACs alongside molecular glue context.

Nanoparticle-assisted targeted protein degraders (NanoTACs) offer a compelling solution by coupling the catalytic efficiency of TPD with the spatial precision and tunability of nanotechnology.

This paper introduces a class of wireless implantable sensors that integrate genetically engineered cells capable of detecting specific molecules for continuous monitoring... We demonstrate a wireless link between a passive, cell-based sensor in a human body phantom and an external receiver.

the response of Escherichia coli is harnessed to trigger the controlled degradation of a passive microwave antenna, which is then monitored via backscatter communication

The ubiquitin-proteasome pathway can be hijacked toward non-native neo-substrate proteins using proteolysis targeting chimeras (PROTACs), bifunctional molecules designed to simultaneously bind to an E3 ligase and a target protein to induce target ubiquitination and degradation.

We evaluate accumulation and degradation kinetics of mRNA encapsulated in Selective Organ Targeting (SORT) LNPs in the liver, lung, and spleen

Spray-induced gene silencing (SIGS), which applies externally produced dsRNA through foliar sprays, seed treatments, or root uptake, provides practical advantages over genetic modification, including rapid deployment, environmental compatibility, and target specificity.

create hypercompact transcript degraders (317 ~ 430 amino acids), named STAR (small toxin- and dEcCas6-CBS-based RNA degraders)

synthetic/epigenetic circuits provide dynamic, context-dependent transgene control that avoids constitutive promoter-driven tonic signaling

here we adapt a receptor architecture called the synthetic intramembrane proteolysis receptor (SNIPR) for activation by soluble ligands

Several types of synthetic receptors have been engineered to deliver specific therapeutic proteins, including ... synthetic intramembrane proteolysis receptors (SNIPRs).

TIP-LITer is a light-inducible TetR-based gene circuit component in which TetR is fused to a Tet-inhibitory peptide through the LOV2 photosensory domain. The reported design places inhibitory peptide control under light-sensitive regulation in mammalian cells.

Combining this error-suppressing strategy with the latest efficiency-boosting architecture, we design a next-generation prime editor (vPE). Compared with previous editors, vPE features comparable efficiency yet up to 60-fold lower indel errors, enabling edit:indel ratios as high as 543:1.

CRY1 is a blue-light-sensing cryptochrome protein from the Arabidopsis cryptochrome family, and the name cry1 is also used for a Drosophila-like insect cryptochrome gene family. The supplied evidence indicates that CRY1 mediates blue light responses, contributes to regulation of early blue light-induced genes, and has functional overlap with CRY2.

Arabidopsis cryptochrome 2 (AtCRY2) is a blue-light-responsive plant photoreceptor domain that has been heterologously expressed in mammalian cells. In that context, blue light induces AtCRY2 photobody formation and also triggers AtCRY2 degradation, providing a light-controlled module linked to protein clustering and turnover.

MALAT1 is a long noncoding RNA reported in trophoblasts to promote cell migration and invasion by reducing CRY2 protein abundance. In the cited study, MALAT1 recruits the E3 ubiquitin ligase FBXW7, impairing CRY2 protein stability and inducing ubiquitin-mediated CRY2 degradation.

Halorhodopsin (NpHR) is a microbial rhodopsin optogenetic tool described as a hyperpolarizing light-driven chloride ion pump. It is used for optical silencing and artificial modulation of neuronal activity, and has been combined with channelrhodopsin-2 (ChR2) for multimodal remote control of neurons in culture, tissue, and living animals.

LOVdeg is an engineered protein tag that is appended to a protein of interest to enable blue-light-inducible degradation in Escherichia coli. It provides optically controlled post-translational regulation by coupling light exposure to loss of the tagged protein.

The photosensitive degron (psd) is a protein-domain tool that confers acute light-induced degradation on fused proteins. Available evidence indicates activity in the nervous system and a construct requirement that the psd be placed at the carboxy terminus of the target protein.

its cognate stem-loop RNA (Cas6 binding site, termed CBS)

The TRIM21 RING domain is a catalytic protein domain whose ubiquitination activity is activated by substrate-induced clustering that promotes intermolecular RING dimerization. In the cited 2020 study, this activation mechanism underlies TRIM21-dependent antiviral responses and Trim-Away-mediated protein degradation.

Synthetically engineered guide RNAs are chemically modified or conjugated CRISPR guide RNAs used in mammalian cells to improve the performance and functional scope of CRISPR-Cas9 systems. Reported implementations increase guide stability and specificity, support donor DNA tethering to enhance homology-directed repair, and enable fluorescent genomic imaging.

The active phytochrome binding (APB) domain is a protein interaction module present in most phytochrome-interacting factors (PIFs) that mediates binding to light-activated phytochrome B (phyB). In Arabidopsis PIF4 and PIF5, this domain is required for phyB-associated, phosphorylation-preceded, proteasome-sensitive degradation in a light-regulated shade-avoidance pathway.

The blue light-inducible degradation (B-LID) domain is a light-activated degron used to trigger loss of a fused protein in vivo. Available evidence indicates that it must be fused to the carboxy terminus of the target protein and can elicit light-dependent loss of Cactus function in developing Drosophila embryos.

The blue light-responsive Cas13b mRNA knockdown system is an optogenetic RNA-control platform in which blue light induces expression of an engineered Cas13b that specifically degrades target mRNAs. In the reported application, combining three blue light-inducible switches reduced protein levels by more than 99%.

The LOV2 domain-based optogenetic tool is a light-responsive protein-domain system reported to control protein degradation and cellular function. The supplied evidence identifies a LOV2-based optogenetic platform but does not specify the exact construct architecture or experimental context.

The photo-N-degron is a peptide tag for optogenetic control of protein function in vivo through light-mediated protein degradation. It was reported to direct light-dependent degradation in Saccharomyces cerevisiae and Drosophila melanogaster, including light-dependent loss of Cactus function in developing Drosophila embryos.

The Jalpha helix is a helical element external to a LOV domain in phototropin proteins that regulates light-dependent kinase signaling. Source literature indicates that unfolding or displacement of the Jalpha helix from the LOV domain activates signaling, and point mutations can induce this displaced state independently of illumination.

The supplied web research summary identifies Azo-PROTAC as an explicitly supported related item candidate and as a major photoswitchable degrader design emphasized by the anchor review.

The use of photoswitchable ligand to control the protein functionalities and related downstream effects in an on-off manner is an active research area in photopharmacology and medicinal chemistry.