TROVE2 Human, His Biotin

What is TROVE2 Human, His Biotin and what is its molecular structure?

TROVE2 Human, His Biotin is a recombinant protein produced in E. coli as a single, non-glycosylated polypeptide chain with a molecular mass of 60kDa. The protein is expressed with a 6xHis tag at its N-terminus and is purified using proprietary chromatographic techniques. Structurally, it maintains the functional aspects of the native human TROVE2 protein (also known as Ro 60 kDa autoantigen) while incorporating the His tag for purification and detection purposes .

The protein is typically supplied in a solution containing 6M Urea, 500mM NaCl, 500mM Imidazole, and 10mM Tris at pH 6.0, which helps maintain its stability. The high purity level (greater than 80% as determined by SDS-PAGE) makes it suitable for a wide range of research applications requiring reliable and consistent results .

What are the alternative names for TROVE2 and why is this important in literature searches?

TROVE2 is known by multiple alternative designations, including 60 kDa SS-A/Ro ribonucleoprotein, 60 kDa ribonucleoprotein Ro, RoRNP, 60 kDa Ro protein, Ro 60 kDa autoantigen, TROVE domain family member 2, Sjoegren syndrome type A antigen (SS-A), and Sjoegren syndrome antigen A2 (SSA2). Other nomenclature includes RO60 and RO-60 .

Understanding these alternative names is critical when conducting comprehensive literature searches, as different research communities may use different terminology. Publications in rheumatology may reference "SS-A antigen," while molecular biology papers might use "TROVE2." Utilizing all synonyms ensures researchers don't miss relevant publications and can properly contextualize their findings across different research domains.

What is the functional role of TROVE2 in cellular processes?

TROVE2 functions primarily as an RNA-binding protein that interacts with several small cytoplasmic RNA molecules known as Y RNAs. Its key physiological role appears to be stabilizing these RNAs from degradation, thus contributing to RNA homeostasis within the cell .

The protein's RNA-binding capacity is mediated through its TROVE domain, which forms a specialized structural motif that allows for specific recognition of Y RNAs. This interaction is critical for various cellular processes including RNA quality control mechanisms and potentially in cellular stress responses. The biological significance of this interaction extends to immune system regulation, as evidenced by the common production of autoantibodies against TROVE2 in several autoimmune conditions .

How should researchers design experiments to study TROVE2-RNA interactions?

When designing experiments to study TROVE2-RNA interactions, researchers should implement a multi-technique approach:

• RNA Immunoprecipitation (RIP): Use anti-His tag antibodies to pull down the His-tagged TROVE2 protein along with bound RNAs. The associated RNAs can then be isolated and analyzed by RT-PCR or sequencing.

• Electrophoretic Mobility Shift Assays (EMSA): Combine purified TROVE2 Human, His Biotin with labeled Y RNAs to observe complex formation through mobility shift in native gels.

• Surface Plasmon Resonance (SPR): Immobilize TROVE2 on a sensor chip and measure binding kinetics of various Y RNAs flowing over the surface to determine association and dissociation constants.

• Microscale Thermophoresis (MST): Label either TROVE2 or Y RNAs and measure changes in thermophoretic mobility upon complex formation to determine binding affinities under near-physiological conditions.

What are the optimal storage and handling conditions for TROVE2 Human, His Biotin?

For TROVE2 Human, His Biotin, optimal storage and handling conditions are critical to maintaining protein integrity and functionality. The protein should be stored at 4°C if the entire vial will be used within 2-4 weeks. For longer-term storage, the protein should be kept frozen at -20°C .

Researchers should strictly avoid multiple freeze-thaw cycles, as these can lead to protein denaturation and loss of activity. When working with the protein, it's advisable to aliquot the stock solution into single-use volumes before freezing to minimize freeze-thaw cycles. The protein solution comes in a buffer containing 6M Urea, 500mM NaCl, 500mM Imidazole, and 10mM Tris at pH 6.0 , which should be considered when designing experiments that may require buffer exchange or dilution.

When performing experiments, maintain sterile conditions as the product is supplied as a sterile filtered clear solution. For optimal results in binding assays or functional studies, pre-equilibrate the protein to room temperature before use and centrifuge briefly to collect all material at the bottom of the tube.

How can TROVE2 Human, His Biotin be utilized in immunoprecipitation assays?

For immunoprecipitation (IP) assays using TROVE2 Human, His Biotin, researchers can employ several strategic approaches:

• Direct IP using anti-His antibodies: Conjugate anti-His antibodies to magnetic or agarose beads and incubate with cell lysates containing expressed TROVE2 Human, His Biotin. This approach allows for the isolation of TROVE2 and its interacting partners.

• Reverse IP for autoantibody studies: Immobilize purified TROVE2 Human, His Biotin on a solid support and incubate with patient sera to capture anti-TROVE2 autoantibodies. This method is particularly useful when studying autoimmune conditions like rheumatoid arthritis or systemic lupus erythematosus.

• RNA immunoprecipitation (RIP): Use TROVE2 Human, His Biotin as bait to capture associated Y RNAs and other RNA species from cellular extracts.

For optimal results, consider the following methodological refinements:

• Pre-clear lysates with naked beads to reduce non-specific binding

• Include appropriate controls (IgG control, lysates without TROVE2 expression)

• Use mild washing conditions to preserve biologically relevant interactions

• Consider crosslinking approaches for capturing transient interactions

• Perform Western blot validation of immunoprecipitated complexes using specific antibodies against expected interacting partners

This approach enables the identification of novel protein-protein interactions and can help elucidate the functional complexes in which TROVE2 participates.

What is the relationship between anti-TROVE2 antibodies and autoimmune diseases?

Anti-TROVE2 antibodies (also known as anti-Ro60/SSA antibodies) are frequently detected in various autoimmune diseases, particularly primary Sjögren's syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). These autoantibodies are found in approximately 3-16.8% of RA patients as reported in various studies .

The presence of these autoantibodies is not merely an epiphenomenon but appears to have functional significance. In SLE patients, sera often contains antibodies that react with the normal cellular SSA2 protein as if this antigen was foreign, suggesting a breakdown in immunological tolerance . The mechanistic relationship involves molecular mimicry and epitope spreading, as research has demonstrated that Ro/SSA and the F(ab') fragment of immunoglobulin G share epitopes that can be bound by anti-Ro/SSA antibodies .

Additionally, anti-Ro60/SSA antibody-positive RA patients typically exhibit B cell activation with a broader autoantibody profile, including polyclonal hypergammaglobulinemia and positive antinuclear antibodies . This suggests that anti-TROVE2 antibodies may serve as markers of a more pronounced dysregulation of humoral immunity in these patients.

How do anti-TROVE2 antibodies impact biologic treatment outcomes in rheumatoid arthritis?

Anti-TROVE2 (anti-Ro60/SSA) antibodies have been identified as significant predictors of treatment outcomes in rheumatoid arthritis patients receiving biologic therapies, particularly adalimumab. Research demonstrates that RA patients with anti-TROVE2 antibodies exhibit a substantially higher rate of poor European League Against Rheumatism (EULAR) responses compared to those without these antibodies .

The mechanism behind this association involves immunogenicity. Patients with anti-TROVE2 antibodies show a significantly higher likelihood of developing anti-drug antibodies (ADAbs) to adalimumab, a fully human monoclonal antibody used in RA treatment. Multivariate logistic regression analysis identified anti-TROVE2 antibody as an independent predictor for ADAb development (odds ratio 70.27, 95% CI 8.17-604.38, p<0.001) after adjusting for potential confounding factors such as age, sex, disease duration, and baseline disease activity .

Furthermore, plasma anti-TROVE2 antibody titers correlate positively with ADAb titers (r=0.79, p<0.005) and negatively with plasma adalimumab levels (r=-0.63, p<0.001) . This inverse relationship with drug levels explains the reduced therapeutic efficacy, as lower concentrations of the active drug reach the intended targets.

This relationship appears specific to biologics with high immunogenicity like adalimumab and infliximab, as similar associations have not been observed with etanercept, abatacept, or tocilizumab, which have lower immunogenicity profiles .

What are the proposed mechanisms explaining the correlation between anti-TROVE2 antibodies and adalimumab immunogenicity?

Several mechanisms have been proposed to explain the strong correlation between anti-TROVE2 antibodies and adalimumab immunogenicity:

• Epitope Sharing: Research suggests that Ro60 (TROVE2) and the F(ab') fragment of immunoglobulin G share epitopes that can be bound by anti-Ro/SSA antibodies . This molecular mimicry could explain why anti-TROVE2 antibodies might directly cross-react with adalimumab, a fully human monoclonal antibody.

• Determinant Spreading: Anti-TROVE2 antibodies may trigger a process called determinant spreading, where the immune response against one epitope expands to include other epitopes within the same protein or even different proteins. Studies have identified multiple T cell and B cell determinants in Ro60 peptides that can enhance autoimmune responses .

• B Cell Hyperreactivity: Patients with anti-Ro/SSA antibodies typically display B cell activation with a spread autoantibody profile, including polyclonal hypergammaglobulinemia and positive antinuclear antibodies . This general B cell hyperreactivity may predispose patients to develop antibodies against therapeutic proteins.

• Altered B Cell Subset Distribution: Recent research reveals that a low percentage of signal regulatory protein α/β+ memory B cells in peripheral blood can predict the development of ADAb to adalimumab , suggesting that anti-TROVE2 positive patients may have distinct B cell population profiles.

These mechanisms likely work in concert, creating an immunological environment conducive to the development of anti-drug antibodies, thereby compromising treatment efficacy in patients with pre-existing anti-TROVE2 antibodies.

How can immunofluorescence assays be optimized for detecting anti-TROVE2 antibodies?

Optimizing immunofluorescence assays for anti-TROVE2 antibody detection requires careful attention to several methodological aspects:

• Substrate Selection: Use HEp-2 cells or TROVE2-transfected cell lines that overexpress the protein to increase sensitivity. For recombinant protein-based assays, immobilize purified TROVE2 Human, His Biotin at optimal concentrations (typically 1-5 μg/mL) on appropriate surfaces.

• Blocking Protocol: Implement a thorough blocking step (1-2 hours) using 3-5% BSA or milk proteins in PBS to minimize background fluorescence and non-specific binding.

• Sample Dilution Series: Prepare patient sera in a dilution series (typically 1:40, 1:80, 1:160, 1:320) to establish optimal working dilutions and determine antibody titers accurately.

• Detection System: Utilize secondary antibodies conjugated with bright, photostable fluorophores (e.g., Alexa Fluor 488 or 594) rather than traditional FITC for improved signal-to-noise ratio.

• Controls Implementation: Include well-characterized positive controls (sera with known anti-TROVE2 antibody titers), negative controls (healthy donor sera), and technical controls (secondary antibody only) in each assay run.

• Standardization Measures: Incorporate calibrators and reference materials with established anti-TROVE2 antibody units to enable quantitative analysis and inter-laboratory comparability.

• Image Acquisition Parameters: Standardize microscope settings including exposure time, gain, and contrast adjustments to ensure consistent results across experiments.

• Automated Analysis: Employ image analysis software with defined algorithms to quantify fluorescence intensity objectively, reducing operator-dependent variability.

Studies have validated that properly optimized immunofluorescence assays can achieve high discriminative power for predicting both ADAb development (AUC 0.79) and poor EULAR response (AUC 0.89) in adalimumab-treated patients .

What biomarker panels incorporating TROVE2 are most effective for predicting therapeutic responses?

Research utilizing immune-related protein microarray and machine learning approaches has identified a panel of 8 biomarkers that demonstrates superior predictive capability for therapeutic responses. This panel includes TROVE2, SSB, NDE1, ZHX2, SH3GL1, CARD9, PTPN20, and KLHL12 .

When subjected to random forest analysis with 1000 iterations, this specific combination achieved 80.6% specificity, 77.4% sensitivity, and 79.0% accuracy in discriminating between patients who would develop anti-drug antibodies (ADAbs) and those who would not . This performance exceeds that of individual biomarkers alone, highlighting the value of a multimarker approach.

Within this panel, anti-TROVE2 antibody consistently demonstrates the highest individual discriminative power. Recursive Feature Elimination (RFE) analysis identified TROVE2 as one of the three most important variables, alongside TPBG and SSB . Notably, all seven top-performing panels identified through extensive testing contained at least TROVE2 and SSB, underscoring their fundamental importance as predictive biomarkers.

For implementation in clinical research settings, this panel can be measured using protein microarray platforms or multiplexed immunoassays. The stability of prediction across multiple iterations suggests that this panel represents a robust tool for stratifying patients according to their likelihood of developing immunogenicity and subsequently experiencing poor therapeutic response.

What are the most reliable methods for quantifying anti-TROVE2 antibody titers in patient samples?

Several methodologies can be employed for reliable quantification of anti-TROVE2 antibody titers, each with specific advantages:

• Fluorescence Immunoassay: This method has demonstrated excellent performance in clinical research settings, achieving high discriminative power for predicting ADAb development (AUC 0.79) and poor EULAR response (AUC 0.89) . The assay involves immobilizing purified TROVE2 protein on a solid phase and detecting bound antibodies using fluorescently-labeled secondary antibodies. Results can be expressed in standard units (U/ml) for quantitative analysis.

• Enzyme-Linked Immunosorbent Assay (ELISA): Specialized ELISA protocols using recombinant TROVE2 Human, His Biotin as the capture antigen provide sensitive and specific detection. The His-tag facilitates uniform orientation of the protein on nickel-coated plates, potentially improving epitope accessibility and assay reproducibility.

• Addressable Laser Bead Immunoassay (ALBIA): This multiplexed approach allows simultaneous detection of multiple autoantibodies including anti-TROVE2. Microspheres coated with purified TROVE2 are incubated with patient samples, and bound antibodies are detected using fluorescently-labeled secondary antibodies.

• Immune-Related Protein Microarray: This high-throughput platform displays thousands of correctly folded functional proteins, enabling comprehensive autoantibody profiling. Studies have utilized this technology to identify anti-TROVE2 antibodies as predictive markers for ADAb development .

For optimal reliability, quantification should include:

• Calibration curves using reference standards with known anti-TROVE2 antibody concentrations

• Internal controls to monitor inter-assay variability

• Established cut-off values derived from ROC analysis of well-characterized patient populations

• Regular proficiency testing to ensure consistent performance

The method selection should be guided by the specific research question, required throughput, and available resources.

How can anti-TROVE2 antibody testing be implemented in clinical practice for rheumatoid arthritis management?

Implementing anti-TROVE2 antibody testing in clinical practice for rheumatoid arthritis would involve a systematic approach:

• Patient Selection: Testing should be conducted before initiating biologic therapies with high immunogenicity profiles, particularly adalimumab and infliximab. Priority should be given to patients with risk factors for treatment failure or those with a history of secondary loss of response to biologics.

• Testing Protocol: Standardized immunofluorescence assays or ELISA-based methods should be employed with established cut-off values. Research has demonstrated that baseline anti-TROVE2 antibody levels serve as independent predictors of ADAb development (OR 70.27, 95% CI 8.17-604.38, p<0.001) and poor EULAR response (OR 55.1, 95% CI 1.9-1596.3, p<0.05) .

• Result Interpretation: Patients with elevated anti-TROVE2 antibody levels (typically >125.0 U/ml) should be flagged as high-risk for developing immunogenicity. These patients showed significantly higher rates of poor EULAR response compared to patients with low antibody levels (median 0.40 U/ml) .

• Clinical Decision Support: For anti-TROVE2 antibody-positive patients, clinicians should consider:

  • Selecting biologics with lower immunogenicity profiles (etanercept, abatacept, tocilizumab)

  • Implementing concomitant methotrexate therapy to reduce immunogenicity

  • More frequent monitoring of disease activity and drug levels

  • Earlier detection of secondary treatment failure

• Monitoring Protocol: For patients who proceed with adalimumab despite positive anti-TROVE2 antibody status, implement proactive monitoring of drug levels and clinical response at 3-month intervals to detect early signs of treatment failure.

This approach transforms the management paradigm from reactive to predictive, potentially improving treatment outcomes and resource utilization by guiding more personalized therapeutic decisions in RA patients.

How do anti-TROVE2 antibody levels change during biologic therapy and what are the implications?

Research examining the dynamics of anti-TROVE2 antibody levels during biologic therapy has yielded important insights. Analysis of anti-TROVE2 levels determined by fluorescence immunoassay after 6 months of adalimumab therapy showed no statistically significant changes (79.0 ± 28.2 U/ml before treatment versus 97.0 ± 30.1 U/ml after treatment) .

This stability of anti-TROVE2 antibody levels has several important implications:

• Predictive Value Maintenance: The consistent levels suggest that the predictive value of baseline anti-TROVE2 antibody testing remains valid throughout the treatment course, supporting its use as a reliable prognostic biomarker.

• Mechanistic Insights: The lack of significant change indicates that adalimumab therapy does not substantially modulate the autoimmune response directed against TROVE2, suggesting that these autoantibodies represent a stable immunological phenotype rather than a treatment-responsive parameter.

• Monitoring Strategy: Since levels remain relatively stable, repeated testing during therapy may not provide additional clinical value beyond the baseline assessment. Resources might be better directed toward monitoring drug levels and anti-drug antibodies in patients identified as high-risk by baseline testing.

• Treatment Decision Timeline: The persistence of anti-TROVE2 antibodies suggests that patients who begin therapy despite positive status should be monitored closely from the outset, rather than waiting for clinical deterioration before implementing enhanced monitoring.

This temporal stability contrasts with the dynamic changes typically observed in anti-drug antibody titers and drug levels, highlighting the distinct nature of anti-TROVE2 antibodies as a pre-existing risk factor rather than a treatment-emergent phenomenon.

What research gaps remain in understanding the relationship between TROVE2 and therapeutic responses?

Despite significant advances, several important research gaps remain in understanding the relationship between TROVE2 and therapeutic responses:

Addressing these research gaps would enhance our understanding of personalized medicine approaches in autoimmune disorders and potentially lead to improved management strategies for patients with anti-TROVE2 antibodies.

What are common challenges when working with TROVE2 Human, His Biotin and how can they be addressed?

Researchers working with TROVE2 Human, His Biotin may encounter several challenges that require specific troubleshooting approaches:

• Protein Aggregation:

  • Challenge: TROVE2 may form aggregates during storage or experimental procedures.

  • Solution: Add low concentrations (0.1-0.5%) of non-ionic detergents like Tween-20 or NP-40 to working solutions. Perform centrifugation (14,000g for 10 minutes) immediately before use to remove any pre-formed aggregates.

• Reduced Activity After Storage:

  • Challenge: Loss of RNA-binding activity after prolonged storage.

  • Solution: Avoid multiple freeze-thaw cycles by preparing single-use aliquots. Monitor protein functionality using simple binding assays before proceeding with complex experiments. Consider adding stabilizing agents such as glycerol (10-15%) to storage buffer.

• His-Tag Interference:

  • Challenge: The His-tag may interfere with certain protein-protein or protein-RNA interactions.

  • Solution: Include appropriate controls with and without His-tag cleavage (using specific proteases like TEV or Factor Xa). Alternatively, validate key findings with native TROVE2 or differently tagged constructs.

• Buffer Compatibility Issues:

  • Challenge: The storage buffer (containing 6M Urea, 500mM NaCl, 500mM Imidazole, and 10mM Tris pH-6) may be incompatible with certain assays.

  • Solution: Perform buffer exchange using dialysis or desalting columns into physiologically relevant buffers. Monitor protein stability and activity following buffer exchange.

• Non-specific Binding in Immunoassays:

  • Challenge: High background in immunoprecipitation or ELISA assays.

  • Solution: Increase blocking agent concentration (5% BSA or milk proteins), include competitors like tRNA or heparin to reduce non-specific RNA-protein interactions, and optimize wash stringency.

By anticipating these challenges and implementing appropriate mitigation strategies, researchers can maximize the reliability and reproducibility of experiments involving TROVE2 Human, His Biotin.

How can researchers optimize experimental design to study contradictory findings about TROVE2 function?

When faced with contradictory findings regarding TROVE2 function, researchers should implement a comprehensive experimental design strategy:

• Multi-system Validation Approach:

  • Employ at least three distinct experimental systems (e.g., recombinant protein assays, cell culture models, and patient-derived samples) to validate findings.

  • Compare results across different cell types relevant to TROVE2 biology (immune cells, epithelial cells).

  • Document differences in experimental outcomes based on the source material or experimental system.

• Dose-Response and Kinetic Analyses:

  • Perform detailed concentration-dependent experiments rather than single-point measurements.

  • Establish time-course studies to capture dynamic changes in TROVE2 function under various conditions.

  • Generate comprehensive response curves to identify potential biphasic effects or threshold phenomena.

• Methodological Triangulation:

  • For any given functional aspect, apply multiple methodological approaches (e.g., studying RNA binding through EMSA, RIP-seq, and crosslinking methods).

  • Quantitatively compare results obtained through different methods to identify technique-specific biases.

• Contextual Variables Assessment:

  • Systematically vary experimental conditions including pH, ionic strength, temperature, and the presence of cofactors.

  • Evaluate the influence of post-translational modifications on TROVE2 function.

  • Test functionality in the presence of relevant binding partners or in reconstituted complexes.

• Hypothesis-Neutral Data Collection:

  • Employ unbiased screening approaches (proteomics, transcriptomics) alongside hypothesis-driven experiments.

  • Pre-register experimental protocols and analysis plans to minimize confirmation bias.

  • Report all outcomes, including negative and inconclusive results.

This systematic approach will help identify the specific conditions or contexts in which apparently contradictory functions manifest, potentially reconciling discrepant findings through a more nuanced understanding of TROVE2 biology.

What emerging technologies could advance our understanding of TROVE2 function and clinical relevance?

Several cutting-edge technologies show promise for advancing TROVE2 research:

• CRISPR-Based Technologies:

  • CRISPR-Cas13 systems can be adapted for RNA visualization to track TROVE2-RNA interactions in living cells.

  • Base editing approaches can introduce specific mutations in TROVE2 to evaluate functional consequences of disease-associated variants.

  • CRISPRi/CRISPRa systems allow precise modulation of TROVE2 expression levels to study dose-dependent effects.

• Single-Cell Multi-omics:

  • Integrated single-cell proteomics and transcriptomics can reveal cell-specific TROVE2 functions and identify distinct cellular states associated with anti-TROVE2 antibody production.

  • Single-cell B cell receptor sequencing in patients with anti-TROVE2 antibodies can track clonal evolution of autoantibody-producing cells.

• Advanced Structural Biology:

  • Cryo-electron microscopy can resolve the structure of TROVE2 in complex with Y RNAs and other binding partners at near-atomic resolution.

  • Hydrogen-deuterium exchange mass spectrometry can map conformational changes in TROVE2 upon RNA binding or autoantibody interaction.

• Proteome-Wide Interaction Mapping:

  • Proximity labeling techniques (BioID, APEX) can identify the protein interactome of TROVE2 in different cellular compartments.

  • Protein-RNA crosslinking followed by mass spectrometry can comprehensively map the RNA-binding sites within TROVE2.

• Machine Learning Applications:

  • Deep learning algorithms applied to patient data can refine prediction models beyond the current panel of 8 biomarkers.

  • Natural language processing of electronic health records can identify previously unrecognized clinical patterns associated with anti-TROVE2 antibody positivity.

These technologies, particularly when applied in combination, have the potential to transform our understanding of TROVE2 biology and accelerate the development of personalized therapeutic approaches for patients with autoimmune disorders.

What potential therapeutic strategies could be developed based on TROVE2 research findings?

TROVE2 research findings point toward several promising therapeutic strategies:

• Biomarker-Guided Treatment Selection:

  • Implementing anti-TROVE2 antibody testing as part of a precision medicine approach to select optimal biologic therapies for individual patients.

  • Patients with high anti-TROVE2 antibody titers could be preferentially directed toward biologics with lower immunogenicity profiles or non-biologic targeted synthetic DMARDs.

• Tolerization Approaches:

  • Developing epitope-specific tolerization protocols targeting the shared epitopes between TROVE2 and therapeutic antibodies.

  • Administration of tolerogenic dendritic cells loaded with specific TROVE2 peptides to induce regulatory T cell responses.

• Immunomodulatory Strategies:

  • Pre-treatment with specific B cell-targeting therapies to reduce anti-TROVE2 antibody production before initiating adalimumab therapy.

  • Developing combination therapies that specifically target memory B cell subsets associated with anti-drug antibody production.

• Engineered Biologics:

  • Designing modified versions of adalimumab with reduced cross-reactivity with anti-TROVE2 antibodies.

  • Creating bispecific antibodies that simultaneously target TNF-α (like adalimumab) and also neutralize anti-TROVE2 antibodies.

• RNA-Based Interventions:

  • Developing Y RNA mimetics that could modulate TROVE2 function and potentially alter autoantigen presentation.

  • Using small interfering RNAs to transiently modulate TROVE2 expression in specific cell populations.