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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Unveiling a classical mutant in the context of the GH 3 β-glucosidase family in Neurospora crassa

Classical fungal mutant strains obtained by mutagenesis have helped to elucidate fundamental metabolic pathways in the past. In the filamentous fungus Neurospora crassa, the gluc-1 strain was isolated long ago and characterized by its low level of β-glucosidase activity, which is essential for the degradation of cellulose, the most abundant biopolymer on Earth and the main polymeric component of the plant cell wall. Based on genomic resequencing, we hypothesized that the causative mutation resides in the β-glucosidase gene gh3-3 (bgl6, NCU08755). In this work, growth patterns, enzymatic activities and sugar utilization rates were analyzed in several mutant and overexpression strains related to gluc-1 and gh3-3. In addition, different mutants affected in the degradation and transport of cellobiose were analyzed. While overexpression of gh3-3 led to the recovery of β-glucosidase activity in the gluc-1 mutant, as well as normal utilization of cellobiose, the full gene deletion strain Δgh3-3 was found to behave differently than gluc-1 with lower secreted β-glucosidase activity, indicating a dominant role of the amino acid substitution in the point mutated gh3-3 gene of gluc-1. Our results furthermore confirm that GH3-3 is the major extracellular β-glucosidase in N. crassa and demonstrate that the two cellodextrin transporters CDT-1 and CDT-2 are essential for growth on cellobiose when the three main N. crassa β-glucosidases are absent. Overall, these findings provide valuable insight into the mechanisms of cellulose utilization in filamentous fungi, being an essential step in the efficient production of biorefinable sugars from agricultural and forestry plant biomass.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Tumorigenic p53 mutants undergo common structural disruptions including conversion to α‐sheet structure

Abstract The p53 protein is a commonly studied cancer target because of its role in tumor suppression. Unfortunately, it is susceptible to mutation‐associated loss of function; approximately 50% of cancers are associated with mutations to p53, the majority of which are located in the central DNA‐binding domain. Here, we report molecular dynamics simulations of wild‐type (WT) p53 and 20 different mutants, including a stabilized pseudo‐WT mutant. Our findings indicate that p53 mutants tend to exacerbate latent structural‐disruption tendencies, or vulnerabilities, already present in the WT protein, suggesting that it may be possible to develop cancer therapies by targeting a relatively small set of structural‐disruption motifs rather than a multitude of effects specific to each mutant. In addition, α‐sheet secondary structure formed in almost all of the proteins. α‐Sheet has been hypothesized and recently demonstrated to play a role in amyloidogenesis, and its presence in the reported p53 simulations coincides with the recent re‐consideration of cancer as an amyloid disease.

Bromley, Dennis↗
DOE OSTI2025

Induced protein expression in Leptospira spp. and its application to CRISPR/Cas9 mutant generation

Abstract Expanding the genetic toolkit for Leptospira spp. is a crucial step toward advancing our understanding of the biology and virulence of these atypical bacteria. Pathogenic Leptospiraare responsible for over 1 million human leptospirosis cases annually and significantly impact domestic animals. Bovine leptospirosis causes substantial financial losses due to abortion, stillbirths, and suboptimal reproductive performance. The advent of the CRISPR/Cas9 system has marked a turning point in genetic manipulation, with applications across multiple Leptospira species. However, incorporating controlled protein expression into existing genetic tools could further expand their utility. We developed and demonstrated the functionality of IPTG-inducible heterologous protein expression in Leptospira spp. This system was applied for regulated expression of dead Cas9 (dCas9) to generate knockdown mutants, and Cas9 to produce knockout mutants by inducing double-strand breaks (DSB) into desired targets. IPTG-induced dCas9 expression enabled validation of essential genes and non-coding RNAs. Additionally, IPTG-controlled Cas9 expression combined with a constitutive non-homologous end-joining (NHEJ) system allowed for successful recovery of knockout mutants, even in the absence of IPTG. These newly controlled protein expression systems will advance studies on the basic biology and virulence ofLeptospira, as well as facilitate knockout mutant generation for improved veterinary vaccines.

Science & Technology - Other Topics↗
DOE OSTI2021

On wavelength-dependent exciton lifetime distributions in reconstituted CP29 antenna of the photosystem II and its site-directed mutants

To provide more insight on the excitonic structure and exciton lifetimes of the wild type (WT) CP29 complex of Photosystem II (PSII) we measured high-resolution (low temperature) absorption, emission, and hole burned spectra for the A2 and B3 mutants, which lack chlorophylls a612 and b614 (Chls), respectively. Experimental and modeling results obtained for the WT CP29 and A2/B3 mutants provide new insight on the mutation-induced changes at the molecular level and shed more light on energy transfer dynamics. Simulations of the A2 and B3 optical spectra, using the second-order non-Markovian theory, and comparison with improved fits of WT CP29 optical spectra, provide more insight on their excitonic structure, mutation induced changes, and frequency-dependent distributions of exciton lifetimes (T 1 ). A new Hamiltonian obtained for WT CP29 reveals that deletion of Chls a612 or b614 induces changes in the site-energies of all remaining Chls. Hamiltonians obtained for A2 and B3 mutants are discussed in the context of the energy landscape of chlorophylls, excitonic structure and the transfer kinetics. Our data suggest that the lowest exciton states in A2 and B3 mutants are contributed by a611(57%), a610(17%), a615(15%) and a615(58%), a611(20%), a612(15%) Chls, respectively, although other compositions of lowest energy states are also discussed. Lastly, we argue that the calculated exciton decay times are consistent with both the hole-burning and recent transient absorption measurements. Wavelength-dependent T 1 distributions offer more insight into the interpretation of kinetic traces commonly described by discrete exponentials in global analysis/global fitting of transient absorption experiments.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Investigating the mechanism of chloroplast singlet oxygen signaling in the Arabidopsis thaliana accelerated cell death 2 mutant

As sessile organisms, plants have evolved complex signaling mechanisms to sense stress and acclimate. This includes the use of reactive oxygen species (ROS) generated during dysfunctional photosynthesis to initiate signaling. One such ROS, singlet oxygen ( 1 O 2 ), can trigger retrograde signaling, chloroplast degradation, and programmed cell death. However, the signaling mechanisms are largely unknown. Several proteins (e.g. PUB4, OXI1, EX1) are proposed to play signaling roles across three Arabidopsis thaliana mutants that conditionally accumulate chloroplast 1 O 2 (fluorescent in blue light (flu), chlorina 1 (ch1), and plastid ferrochelatase 2 (fc2)). We previously demonstrated that these mutants reveal at least two chloroplast 1 O 2 signaling pathways (represented by flu and fc2/ch1). Here, we test if the 1 O 2 -accumulating lesion mimic mutant, accelerated cell death 2 (acd2), also utilizes these pathways. The pub4–6 allele delayed lesion formation in acd2 and restored photosynthetic efficiency and biomass. Conversely, an oxi1 mutation had no measurable effect on these phenotypes. acd2 mutants were not sensitive to excess light (EL) stress, yet pub4–6 and oxi1 both conferred EL tolerance within the acd2 background, suggesting that EL-induced 1 O 2 signaling pathways are independent from spontaneous lesion formation. Thus, 1 O 2 signaling in acd2 may represent a third (partially overlapping) pathway to control cellular degradation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Proteomic Insights into Trichome Responses to Elevated Elemental Stress in Cation Exchanger (CAX) Mutants

Abstract Research on elemental distribution in plants is crucial for understanding nutrient uptake, environmental adaptation and optimizing agricultural practices for sustainable food production. Plant trichomes, with their self-contained structures and easy accessibility, offer a robust model system for investigating elemental repartitioning. Transport proteins, such as the four functional cation exchangers (CAXs) in Arabidopsis, are low-affinity, high-capacity transporters primarily located on the vacuole. Mutants in these transporters have been partially characterized, one of the phenotypes of the CAX1 mutant being altered with tolerance to low-oxygen conditions. A simple visual screen demonstrated trichome density and morphology in cax1, and quadruple CAX (cax1-4: qKO) mutants remained unaltered. Here, we used synchrotron X-ray fluorescence (SXRF) to show that trichomes in CAX-deficient lines accumulated high levels of chlorine, potassium, calcium and manganese. Proteomic analysis on isolated Arabidopsis trichomes showed changes in protein abundance in response to changes in element accumulation. The CAX mutants showed an increased abundance of plasma membrane ATPase and vacuolar H-pumping proteins, and proteins associated with water movement and endocytosis, while also showing changes in proteins associated with the regulation of plasmodesmata. These findings advance our understanding of the integration of CAX transport with elemental homeostasis within trichomes and shed light on how plants modulate protein abundance under conditions of altered elemental levels.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Rewired phenolic metabolism and improved saccharification efficiency of a Zea mays cinnamyl alcohol dehydrogenase 2 (zmcad2) mutant

Lignocellulosic biomass is an abundant byproduct from cereal crops that can potentially be valorized as a feedstock to produce biomaterials. Zea mays CINNAMYL ALCOHOL DEHYDROGENASE 2 (ZmCAD2) is involved in lignification, and is a promising target to improve the cellulose–to–glucose conversion of maize stover. Here, we analyzed a field–grown zmcad2 Mutator transposon insertional mutant. Zmcad2 mutant plants had an 18% lower Klason lignin content, whereas their cellulose content was similar to that of control lines. The lignin in zmcad2 mutants contained increased levels of hydroxycinnamaldehydes, i.e. the substrates of ZmCAD2, ferulic acid and tricin. Ferulates decorating hemicelluloses were not altered. Phenolic profiling further revealed that hydroxycinnamaldehydes are partly converted into (dihydro)ferulic acid and sinapic acid and their derivatives in zmcad2 mutants. Syringyl lactic acid hexoside, a metabolic sink in CAD–deficient dicot trees, appeared not to be a sink in zmcad2 maize. The enzymatic cellulose–to–glucose conversion efficiency was determined after 10 different thermochemical pre–treatments. Zmcad2 yielded significantly higher conversions compared with controls for almost every pre–treatment. However, the relative increase in glucose yields after alkaline pre–treatment was not higher than the relative increase when no pre–treatment was applied, suggesting that the positive effect of the incorporation of hydroxycinnamaldehydes was leveled off by the negative effect of reduced p–coumarate levels in the cell wall. Here, taken together, our results reveal how phenolic metabolism is affected in CAD–deficient maize, and further support mutating CAD genes in cereal crops as a promising strategy to improve lignocellulosic biomass for sugar–platform biorefineries.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Silencing of Dicer‐like protein 2a restores the resistance phenotype in the rice mutant, sxi4 ( suppressor of Xa21‐mediated immunity 4 )

SUMMARY The rice immune receptor XA21 confers resistance to Xanthomonas oryzae pv. oryzae ( Xoo ), and upon recognition of the RaxX21‐sY peptide produced by Xoo , XA21 activates the plant immune response. Here we screened 21 000 mutant plants expressing XA21 to identify components involved in this response, and reported here the identification of a rice mutant, sxi4, which is susceptible to Xoo. The sxi4 mutant carries a 32‐kb translocation from chromosome 3 onto chromosome 7 and displays an elevated level of DCL2a transcript, encoding a Dicer‐like protein . Silencing of DCL2a in the sxi4 genetic background restores resistance to Xoo . RaxX21‐sY peptide‐treated leaves of sxi4 retain the hallmarks of XA21‐mediated immune response. However, WRKY45‐1 , a known negative regulator of rice resistance to Xoo , is induced in the sxi4 mutant in response to RaxX21‐sY peptide treatment. A CRISPR knockout of a short interfering RNA (TE‐siRNA815) in the intron of WRKY45‐1 restores the resistance phenotype in sxi4 . These results suggest a model where DCL2a accumulation negatively regulates XA21‐mediated immunity by altering the processing of TE‐siRNA815.

Liu, Furong↗
DOE OSTI2026

Discovery of BBO-11818, a Potent and Selective Noncovalent Inhibitor of (ON) and (OFF) KRAS with Activity against Multiple Oncogenic Mutants

Although KRAS G12C -specific inhibitors have been introduced, no approved targeted therapies exist for other clinically significant KRAS mutants, including KRAS G12D and KRAS G12V . We discovered BBO-11818, a potent, selective, orally bioavailable noncovalent pan-KRAS inhibitor capable of targeting multiple KRAS mutants in both the inactive GDP-bound (OFF) and active GTP-bound (ON) states. BBO-11818 binds in the Switch-II/Helix 3 pocket, inducing conformational changes incompatible with effector binding, and demonstrates high-affinity binding to mutant KRAS with strong selectivity over NRAS and HRAS. BBO-11818 potently inhibited MAPK signaling and cellular viability specifically in KRAS-driven lines and produced tumor regressions in KRAS-mutant xenograft models. Combination studies with anti–PD-1, anti-EGFR antibodies, and a RAS:PI3Kα breaker compound showed enhanced efficacy. BBO-11818 has entered phase I clinical trials for patients with various KRAS mutations in colorectal, pancreatic, and lung cancers (NCT06917079).

Stahlhut, Carlos [BridgeBio Oncology Therapeutics,↗
DOE OSTI2022

Comparative Phenotyping of Two Commonly Used Chlamydomonas reinhardtii Background Strains: CC-1690 (21gr) and CC-5325 (The CLiP Mutant Library Background)

The unicellular green alga Chlamydomonas reinhardtii is an excellent model organism to investigate many essential cellular processes in photosynthetic eukaryotes. Two commonly used background strains of Chlamydomonas are CC-1690 and CC-5325. CC-1690, also called 21gr, has been used for the Chlamydomonas genome project and several transcriptome analyses. CC-5325 is the background strain for the Chlamydomonas Library Project (CLiP). Photosynthetic performance in CC-5325 has not been evaluated in comparison with CC-1690. Additionally, CC-5325 is often considered to be cell-wall deficient, although detailed analysis is missing. The circadian rhythms in CC-5325 are also unclear. To fill these knowledge gaps and facilitate the use of the CLiP mutant library for various screens, we performed phenotypic comparisons between CC-1690 and CC-5325. Our results showed that CC-5325 grew faster heterotrophically in dark and equally well in mixotrophic liquid medium as compared to CC-1690. CC-5325 had lower photosynthetic efficiency and was more heat-sensitive than CC-1690. Furthermore, CC-5325 had an intact cell wall which had comparable integrity to that in CC-1690 but appeared to have reduced thickness. Additionally, CC-5325 could perform phototaxis, but could not maintain a sustained circadian rhythm of phototaxis as CC1690 did. Finally, in comparison to CC-1690, CC-5325 had longer cilia in the medium with acetate but slower swimming speed in the medium without nitrogen and acetate. Our results will be useful for researchers in the Chlamydomonas community to choose suitable background strains for mutant analysis and employ the CLiP mutant library for genome-wide mutant screens under appropriate conditions, especially in the areas of photosynthesis, thermotolerance, cell wall, and circadian rhythms.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1998

Analysis of mutant quantity and quality in human-hamster hybrid AL and AL-179 cells exposed to 137Cs-gamma or HZE-Fe ions

We measured the number of mutants and the kinds of mutations induced by 137Cs-gamma and by HZE-Fe (56Fe [600 MeV/amu, LET = 190 KeV/micrometer) in standard AL human hamster hybrid cells and in a new variant hybrid, AL-179. We found that HZE-Fe was more mutagenic than 137Cs-gamma per unit dose (about 1.6 fold), but was slightly less mutagenic per mean lethal dose, DO, at both the S1 and hprt- loci of AL cells. On the other hand, HZE-Fe induced about nine fold more complex S1- mutants than 137Cs-gamma rays, 28% vs 3%. 137Cs-gamma rays induced about twice as many S1- mutants and hprt-mutants in AL-179 as in AL cells, and about nine times more of the former were complex, and potentially unstable kinds of mutations.

NASA Discipline Radiation Health↗
NASA NTRS1990

A direct screening procedure for gravitropism mutants in Arabidopsis thaliana (L.) Heynh

In order to isolate gravitropism mutants of Arabidopsis thaliana (L.) Heynh. var Estland for the genetic dissection of the gravitropism pathway, a direct screening procedure has been developed in which mutants are selected on the basis of their gravitropic response. Variability in hypocotyl curvature was dependent on the germination time of each seed stock, resulting in the incorrect identification of several lines as gravitropism mutants when a standard protocol for the potentiation of germination was used. When the protocol was adjusted to allow for differences in germination time, these lines were eliminated from the collection. Out of the 60,000 M2 seedlings screened, 0.3 to 0.4% exhibited altered gravitropism. In approximately 40% of these mutant lines, only gravitropism by the root or the hypocotyl was altered, while the response of the other organ was unaffected. These data support the hypothesis that root and hypocotyl gravitropism are genetically separable.

NASA Discipline Number 29-20↗
NASA NTRS1989

Root graviresponsiveness and cellular differentiation in wild-type and a starchless mutant of Arabidopsis thaliana

Primary roots of a starchless mutant of Arabidopsis thaliana L. are strongly graviresponsive despite lacking amyloplasts in their columella cells. The ultrastructures of calyptrogen and peripheral cells in wild-type as compared to mutant seedlings are not significantly different. The largest difference in cellular differentiation in caps of mutant and wild-type roots is the relative volume of plastids in columella cells. Plastids occupy 12.3% of the volume of columella cells in wild-type seedlings, but only 3.69% of columella cells in mutant seedlings. These results indicate that: (1) amyloplasts and starch are not necessary for root graviresponsiveness; (2) the increase in relative volume of plastids that usually accompanies differentiation of columella cells is not necessary for root graviresponsiveness; and (3) the absence of starch and amyloplasts does not affect the structure of calyptrogen (i.e. meristematic) and secretory (i.e. peripheral) cells in root caps. These results are discussed relative to proposed models for root gravitropism.

NASA Program Space Biology↗
NASA NTRS2001

p53 deficiency alters the yield and spectrum of radiation-induced lacZ mutants in the brain of transgenic mice

Exposure to heavy particle radiation in the galacto-cosmic environment poses a significant risk in space exploration and the evaluation of radiation-induced genetic damage in tissues, especially in the central nervous system, is an important consideration in long-term manned space missions. We used a plasmid-based transgenic mouse model system, with the pUR288 lacZ transgene integrated in the genome of every cell of C57Bl/6(lacZ) mice, to evaluate the genetic damage induced by iron particle radiation. In order to examine the importance of genetic background on the radiation sensitivity of individuals, we cross-bred p53 wild-type lacZ transgenic mice with p53 nullizygous mice, producing lacZ transgenic mice that were either hemizygous or nullizygous for the p53 tumor suppressor gene. Animals were exposed to an acute dose of 1 Gy of iron particles and the lacZ mutation frequency (MF) in the brain was measured at time intervals from 1 to 16 weeks post-irradiation. Our results suggest that iron particles induced an increase in lacZ MF (2.4-fold increase in p53+/+ mice, 1.3-fold increase in p53+/- mice and 2.1-fold increase in p53-/- mice) and that this induction is both temporally regulated and p53 genotype dependent. Characterization of mutants based on their restriction patterns showed that the majority of the mutants arising spontaneously are derived from point mutations or small deletions in all three genotypes. Radiation induced alterations in the spectrum of deletion mutants and reorganization of the genome, as evidenced by the selection of mutants containing mouse genomic DNA. These observations are unique in that mutations in brain tissue after particle radiation exposure have never before been reported owing to technical limitations in most other mutation assays.

Non-NASA Center↗
NASA NTRS1999

Plastid sedimentation kinetics in roots of wild-type and starch-deficient mutants of Arabidopsis

Sedimentation and movement of plastids in columella cells of the root cap were measured in seedlings of wild-type, a reduced starch mutant, and a starchless mutant of Arabidopsis. To assay for sedimentation, we used both linear measurements and the change of angle from the cell center as indices in vertical and reoriented plants with the aid of computer-assisted image analysis. Seedlings were fixed at short periods after reorientation, and plastid sedimentation correlated with starch content in the three strains of Arabidopsis. Amyloplasts of wild-type seedlings showed the greatest sedimentation, whereas plastids of the starchless mutant showed no significant sedimentation in the vertically grown and reoriented seedlings. Because previous research has shown that a full complement of starch is needed for full gravitropic sensitivity, this study correlates increased sensitivity with plastid sedimentation. However, although plastid sedimentation contributed to gravisensitivity, it was not required, because the gravitropic starchless mutant had plastids that did not sediment. This is the first study, to our knowledge, to measure plastid sedimentation in Arabidopsis roots after reorientation of seedlings. Taken together, the results of this study are consistent with the classic plastid-based and protoplast-based models of graviperception and suggest that multiple systems of perception exist in plant cells.

NASA Discipline Plant Biology↗
NASA NTRS1998

Light promotion of hypocotyl gravitropism of a starch-deficient tobacco mutant correlates with plastid enlargement and sedimentation

Dark-grown hypocotyls of a starch-deficient mutant (NS458) of tobacco (Nicotiana sylvestris) lack amyloplasts and plastid sedimentation, and have severely reduced gravitropism. However, gravitropism improved dramatically when NS458 seedlings were grown in the light. To determine the extent of this improvement and whether mutant hypocotyls contain sedimented amyloplasts, gravitropic sensitivity (induction time and intermittent stimulation) and plastid size and position in the endodermis were measured in seedlings grown for 8 d in the light. Light-grown NS458 hypocotyls were gravitropic but were less sensitive than the wild type (WT). Starch occupied 10% of the volume of NS458 plastids grown in both the light and the dark, whereas WT plastids were essentially filled with starch in both treatments. Light increased plastid size twice as much in the mutant as in the WT. Plastids in light-grown NS458 were sedimented, presumably because of their larger size and greater total starch content. The induction by light of plastid sedimentation in NS458 provides new evidence for the role of plastid mass and sedimentation in stem gravitropic sensing. Because the mutant is not as sensitive as the WT, NS458 plastids may not have sufficient mass to provide full gravitropic sensitivity.

Non-NASA Center↗
NASA NTRS1997

Reduced gravitropism in hypocotyls of starch-deficient mutants of Arabidopsis

Gravitropism was examined in dark- and light-grown hypocotyls of wild-type (WT), two reduced starch mutants (ACG 20 and ACG 27), and a starchless mutant (ACG 21) of Arabidopsis. In addition, the starch content of these four strains was studied with light and electron microscopy. Based on time course of curvature and orientation studies, the graviresponse in hypocotyls is proportional to the amount of starch in a genotype. Furthermore, starch mutations seem to primarily affect gravitropism rather than differential growth since both phototropic curvature and growth rates among the four genotypes are approximately equal. Our results suggest that gravity perception may require a greater plastid mass in hypocotyls compared to roots. The kinetics of gravitropic curvature also was compared following reorientation at 45 degrees, 90 degrees, and 135 degrees. As has been reported for other plant species, the optimal angle of reorientation is 135 degrees for WT Arabidopsis and the two reduced starch mutants, but the magnitude of curvature of the starchless mutant appears to be independent of the initial angle of displacement. Taken together, the results of the present study and our previous experiments with roots of the same four genotypes [Kiss et al. (1996) Physiol. Plant. 97: 237] support a plastid-based hypothesis for gravity perception in plants.

Non-NASA Center↗
DOE OSTI2021

FAK-targeting PROTAC demonstrates enhanced antitumor activity against KRAS mutant non-small cell lung cancer

Focal adhesion kinase (FAK) has been established as a promising therapeutic target for KRAS mutant non-small cell lung cancer (NSCLC). However, phase II clinical trials of a FAK inhibitor (Defactinib) have only shown modest antitumor activity. To address this challenge, here we report the use of a FAK-targeting proteolysis targeting chimera (D-PROTAC) to treat KRAS mutant NSCLC. We validated that D-PROTAC could efficiently eliminate FAK protein via the ubiquitin-proteasome pathway in KRAS mutant NSCLC A427 cells, causing over 90% degradation at 800 nM. After comparing both in vitro and in vivo therapeutic efficacies, we demonstrated that D-PRTOAC outperformed Defactinib in inhibiting tumor growth. Specifically, D-PROTAC at 800 nM reduced cell viability, migration, and invasion by ∼80%. Furthermore, a ∼85% suppression of tumor growth was elicited by D-PROTAC when intratumorally administrated at 10 mg/kg in subcutaneous A427-bearing mice. These results thus demonstrate for the first time that PROTACs may serve as promising therapeutic agents for the intractable NSCLC harboring KRAS mutations.

60 APPLIED LIFE SCIENCES↗