Activation of this pathway, termed EJC-dependent NMD, requires that exon junction complexes exist downstream of ribosomes stalled at PTCs during the first round of translation. Although activation of fail-safe NMD does not rely on the presence of an intron downstream of the PTC, it requires the presence of an intron elsewhere in the gene. In addition, mechanisms that, for example, alter splicing can inactivate PTC-containing Armepavine transcripts without leading to their degradation. In this regard, pre-mRNAs with PTCs can accumulate un-spliced, or incompletely spliced, in the nucleus. Moreover, PTC-containing transcripts can be alternatively spliced removing the exon with the PTC, a process termed nonsense-associated altered splicing. How PTCs are sensed in these incompletely processed transcripts is not completely understood. Together, these mechanisms prevent transcripts with PTCs from encoding truncated proteins that could have detrimental effects. T cell receptor beta chain locus transcripts containing PTCs are readily destroyed by NMD in vivo. Here, we develop an approach to directly determine the requirement for an intron downstream of the PTC in efficiently clearing transcripts templated by the endogenous Tcrb locus in thymocytes. When nanoparticles are exposed to biological fluids via systemic administration or ex vivo incubation, they interact with proteins to form a biological coating on the AuNP to form a protein coating or corona. This corona dictates the biological response, as well as many physical properties, of the AuNP. Identifying the contents of the protein corona can provide unique insight into the biological function of the AuNPs, including their biodistribution, clearance, and potential toxicity. In addition to affecting nanoparticle behavior, the process of corona formation provides a tool for probing the local proteome. As such, protein-covered nanoparticles may also provide insight into disease states and thereby help to identify new therapeutic targets. Formation of the protein corona will depend on the nature of the interaction between the nanoparticles/conjugates and the biological fluids chosen, as dictated by the surface properties of the nanoparticles. The nature of the interaction will depend mainly on i) the charge of the nanoconjugate, i.e., positive, negative, zwitterionic, or neutral and ii) the hydrophobicity/ hydrophilicity of the conjugate. In this manuscript, we examine the nature of the protein corona captured by surface-functionalized AuNPs when exposed to clinically relevant biological fluids, and reveal that tuning the nanoparticle surface charge can preferentially Amantadine hydrochloride enrich and therefore enable detection of otherwise undetected low-abundance proteins as possible therapeutic targets. We used a combination of UV-Visible spectroscopy, dynamic light scattering, zeta potential measurement, and Bradford protein assay to characterize the protein corona.