Virus-like particles (VLPs) are nanoscale biological structures consisting of viral proteins assembled in a morphology that mimic the native virion but do not contain the viral genetic material. The possibility of chemically and genetically modifying the proteins contained within VLPs makes them an attractive system for numerous applications. As viruses are potent immune activators as well as natural delivery vehicles of genetic materials to their host cells, VLPs are especially well suited for antigen and drug delivery applications. Despite the great potential, very few VLP designs have made it through clinical trials. In this review, we will discuss the challenges of developing VLPs for antigen and drug delivery, strategies being explored to address these challenges, and the genetic and chemical approaches available for VLP engineering.

Protein therapeutics is a rapidly growing segment of the pharmaceutical market. Currently, the majority of protein therapeutics are manufactured in mammalian cells for their ability to generate safe and efficacious human-like glycoproteins. The high cost of using mammalian cells for manufacturing has motivated a constant search for alternative host platforms. Insect cells have begun to emerge as a promising candidate, largely due to the development of the baculovirus expression vector system. While there are continuing efforts to improve insect-baculovirus expression for producing protein therapeutics, key limitations including cell lysis and the lack of homogeneous humanized glycosylation still remain. The field has started to see a movement toward virus-less gene expression approaches, notably the use of clustered regularly interspaced short palindromic repeats to address these shortcomings. This review highlights recent technological advances that are realizing the transformative potential of insect cells for the manufacturing and development of protein therapeutics.

To provide broader protection and eliminate the need for annual update of influenza vaccines, biomolecular engineering of influenza virus-like particles (VLPs) to display more conserved influenza proteins such as the matrix protein M2 has been explored. However, achieving high surface density of full-length M2 in influenza VLPs has been left unrealized. In this study, we show that the ion channel activity of M2 induces significant cytopathic effects in Spodoptera f rugiperda (Sf9) insect cells when expressed using M2encoding baculovirus. These effects include altered Sf9 cell morphology and reduced baculovirus replication, resulting in impaired influenza protein expression and thus VLP production. On the basis of the function of M2, we hypothesized that blocking its ion channel activity could potentially relieve these cytopathic effects, and thus restore influenza protein expression to improve VLP production. The use of the M2 inhibitor amantadine indeed improves Sf9 cellular expression not only of M2 (∼3-fold), but also of hemagglutinin (HA) (∼7-fold) and of matrix protein M1 (∼3-fold) when coexpressed to produce influenza VLPs. This increased cellular expression of all three influenza proteins further leads to ∼2-fold greater VLP yield. More importantly, the quality of the resulting influenza VLPs is significantly improved, as demonstrated by the ∼2-fold, ∼50-fold, and ∼2-fold increase in the antigen density to approximately 53 HA, 48 M1, and 156 M2 per influenza VLP, respectively. Taken together, this study represents a novel approach to enable the efficient incorporation of full-length M2 while enhancing both the yield and quality of influenza VLPs produced by Sf9 cells.

Over the past decade, the increasingly globalized society has continually redefined the qualities and skills of an ideal engineering graduate for industry and academic careers, and, more recently, in light of a global pandemic in 2020, the pedagogical environment has shifted toward a virtual classroom setting. Because the engineering and social challenges of the modern world are rapidly evolving, it is important to adapt teaching methods that reflect these changing times. An increasingly attractive teaching method in the engineering classroom is project-based learning (PBL), which is known to improve engaged-learning outcomes, such as creativity, risk taking, social responsibility, teamwork, self-confidence, and communication. However, it is still unclear how various PBL practices differentially impact these engaged-learning outcomes. Toward the goal of elucidating this, the impact of two different project formats, a virtual presentation versus an in-person presentation, was evaluated for a junior-level chemical engineering core course, Mass and Heat Transfer, over 2 years (248 students total). In surveys conducted after the projects were completed, students were asked to what degree the project improved each of the learning outcomes on a scale of 0 (no impact) to 10 (great impact). Data from these postproject surveys showed no statistically significant differences in impact on teamwork, self-confidence, and communication skills between the two groups. However, the virtual presentation had statistically significant greater positive impacts on student creativity [mean score: 8.9/10 (virtual) vs 7.7/10 (in-person); p < 0.001] and risk taking [mean score: 7.7/10 (virtual) vs 6.1/10 (in-person); p < 0.001], whereas the in-person presentation had a significantly more positive impact on social responsibility [mean score: 6.5/10 (in-person) vs 5.5/10 (virtual); p < 0.05]. Qualitative insights into these results were gathered from discussions with students in focus groups. The results of this study underscore the unique advantages associated with different presentation formats. From the perspective of the current transitions to online learning, the results suggest that changing project deliverables from an in-person to a virtual format may actually yield net gains in engaged-learning outcomes.