The use of metal–organic frameworks (MOFs) in biomedical applications has greatly expanded over the past decade due to the precision tunability, high surface areas, and high loading capacities of MOFs. Specifically, MOFs are being explored for a wide variety of drug delivery applications. Initially, MOFs were used for delivery of small-molecule pharmaceuticals; however, more recent work has focused on macromolecular cargos, such as proteins and nucleic acids. Here, we review the historical application of MOFs for drug delivery, with a specific focus on the available options for designing MOFs for specific drug delivery applications. These options include choices of MOF structure, synthetic method, and drug loading. Further considerations include tuning, modifications, biocompatibility, cellular targeting, and uptake. Altogether, this Review aims to guide MOF design for novel biomedical applications.

This longitudinal study investigated development in expectancy for success (perceived competence), 3 types of task value (utility, interest, attainment), and 3 types of perceived cost (opportunity, effort, psychological) for engineering students during their first 2 years of college. Latent growth curve models indicated declines in expectancy and values, with attainment value declining more slowly than expectancy, interest value, and utility value. Costs increased over time, with effort cost increasing more rapidly than psychological cost. Demographic differences were observed in initial levels of motivation, but not in rates of change over time. Students with slower declines in expectancy and value and slower increases in effort cost achieved higher grades and were more likely to remain in an engineering major. The attainment value model explained the largest amount of variance in engineering major retention, while the expectancy model explained the largest amount of variance in GPA. Taking a supportive gateway course in the first semester rather than later was associated with slower declines in utility value and attainment value, and slower increases in effort cost. Results suggest expectancy, values, and costs display unique patterns of development and uniquely relate to predictors and outcomes, extending our theoretical understanding of motivation in early college. Implications for practice include the promise of programmatic efforts to support students’ motivation in engineering through supportive gateway courses early in college.

The recognition of small interfering RNAs (siRNAs) by the RNA induced silencing complex (RISC) and its precursor, the RISC loading complex (RLC), is a key step in the RNA interference pathway that controls the subsequent sequence-specific mRNA degradation. In Drosophila, selection of the guide strand has been shown to be mediated by the RLC protein R2D2, which senses the relative hybridization stability between the two ends of the siRNA. A protein with similar function has yet to be conclusively identified in humans. We show here that human TAR RNA binding protein (TRBP) alone can bind siRNAs in vitro and sense their asymmetry. We also show that TRBP can bind 21 nucleotide single-stranded RNAs, though with far lower affinity than for double-stranded siRNA, and that TRBP crosslinks preferentially to the 3′ ends of the guide strands of siRNAs. This suggests that TRBP binding depends both on the sequences of the siRNA strands as well as the relative hybridization stability of the ends of the duplex. Together these results demonstrate the importance of the siRNA-TRBP interaction in the selection of the siRNA guide strand in RNAi.

The selection of active siRNAs is generally based on identifying siRNAs with certain sequence and structural properties. However, the efficiency of RNA interference has also been shown to depend on the structure of the target mRNA, primarily through studies using exogenous transcripts with welldefined secondary structures in the vicinity of the target sequence. While these studies provide a means for examining the impact of target sequence and structure independently, the predicted secondary structures for these transcripts are often not reflective of structures that form in full-length, native mRNAs where interactions can occur between relatively remote segments of the mRNAs. Here, using a combination of experimental results and analysis of a large dataset, we demonstrate that the accessibility of certain local target structures on the mRNA is an important determinant in the gene silencing ability of siRNAs. siRNAs targeting the enhanced green fluorescent protein were chosen using a minimal siRNA selection algorithm followed by classification based on the predicted minimum free energy structures of the target transcripts. Transfection into HeLa and HepG2 cells revealed that siRNAs targeting regions of the mRNA predicted to have unpaired 5'-and 3'-ends resulted in greater gene silencing than regions predicted to have other types of secondary structure. These results were confirmed by analysis of gene silencing data from previously published siRNAs, which showed that mRNA target regions unpaired at either the 5'-end or 3'-end were silenced, on average, ~10% more strongly than target regions unpaired in the center or primarily paired throughout. We found this effect to be independent of the structure of the siRNA guide strand. Taken together, these results suggest minimal requirements for nucleation of hybridization between the siRNA guide strand and mRNA and that both mRNA and guide strand structure should be considered when choosing candidate siRNAs.