A telehealth-based interprofessional education module focused on social determinants of health.

BACKGROUND: This report describes a telehealth-based interprofessional education (IPE) module that connected medical and pharmacy students across different geographical locations. The IPE module focused on developing strategies aimed at reducing health inequities related to social determinants of health. INTERPROFESSIONAL EDUCATION ACTIVITY: Teams of one doctor of osteopathic medicine and one or two doctor of pharmacy students were created by the course faculty member. Teams were instructed to meet at least four times via videoconferencing technology to discuss their assigned health inequity. Teams were instructed to design possible interventions to reduce the health inequity in their communities. Students completed the Interprofessional Collaborative Competency Attainment Scale (ICCAS) and a peer evaluation to provide feedback to their team member(s). DISCUSSION: Four hundred and seventy teams comprising 1099 students have participated in this IPE module. On the ICCAS, significant improvement was noted on all items with highest gains on items related to communication and collaboration. On the 2018-2019 peer evaluations, 84.5% of students rated their teammates as exceptional on the item "rate your team member's respect for you and others on the team." On the 2019-2020 peer evaluations, highest agreement was noted on the statement "this student is able to act with honesty and integrity in relationships with other team members." A total of 81% of students felt that the IPE module was useful to their learning. IMPLICATIONS: Improvement in the ICCAS and positive peer evaluations support a telehealth-based model for provision of IPE.

Targeted gene delivery to CD117-expressing cells in vivo with lentiviral vectors co-displaying stem cell factor and a fusogenic molecule.

The development of a lentiviral system to deliver genes to specific cell types could improve the safety and the efficacy of gene delivery. Previously, we have developed an efficient method to target lentivectors to specific cells via an antibody-antigen interaction in vitro and in vivo. We report herein a targeted lentivector that harnesses the natural ligand-receptor recognition mechanism for targeted modification of c-KIT receptor-expressing cells. For targeting, we incorporate membrane-bound human stem cell factor (hSCF), and for fusion, a Sindbis virus-derived fusogenic molecule (FM) onto the lentiviral surface. These engineered vectors can recognize cells expressing surface CD117, resulting in efficient targeted transduction of cells in an SCF-receptor dependent manner in vitro, and in vivo in xenografted mouse models. This study expands the ability of targeting lentivectors beyond antibody targets to include cell-specific surface receptors. Development of a high titer lentivector to receptor-specific cells is an attractive approach to restrict gene expression and could potentially ensure therapeutic effects in the desired cells while limiting side effects caused by gene expression in non-target cells.

Cell type-specific targeting with surface-engineered lentiviral vectors co-displaying OKT3 antibody and fusogenic molecule.

PURPOSE: The purpose of this study was to investigate the potential of a T-cell-related targeting method using a lentiviral vector-based gene delivery system. MATERIALS AND METHODS: A lentiviral vector system was constructed by co-incorporating an anti-CD3 antibody (OKT3) and a fusogen into individual viral particles. The incorporation of OKT3 and fusogen was analyzed using confocal microscopy and the in vitro transduction efficiency was evaluated using flow cytometry. Blocking reagents (ammonium chloride (NH(4)Cl) and soluble OKT3 antibody) were added into vector supernatants during transduction to study the mechanism of this two-molecule targeting strategy. To demonstrate the ability of targeted transduction in vivo, Jurkat.CD3 cells were xenografted subcutaneously into the right flank of each mouse and the lentiviral vector was injected subcutaneously on both sides of each mouse 8 h post-injection. Subsequently, the reporter gene (firefly luciferase) expression was monitored using a noninvasive bioluminescence imaging system. RESULTS: By co-displaying OKT3 and fusogen on the single lentiviral surface, we could achieve targeted delivery of genes to CD3-positive T-cells both in vitro and in vivo. CONCLUSIONS: These results suggest the potential utility of this engineered lentiviral system as a new tool for cell type-directed gene delivery.

Targeting lentiviral vectors to antigen-specific immunoglobulins.

Gene transfer into B cells by lentivectors can provide an alternative approach to managing B lymphocyte malignancies and autoreactive B cell-mediated autoimmune diseases. These pathogenic B cell populations can be distinguished by their surface expression of monospecific immunoglobulin. Development of a novel vector system to deliver genes to these specific B cells could improve the safety and efficacy of gene therapy. We have developed an efficient method to target lentivectors to monospecific immunoglobulin-expressing cells in vitro and in vivo. We were able to incorporate a model antigen CD20 and a fusogenic protein derived from the Sindbis virus as two distinct molecules into the lentiviral surface. This engineered vector could specifically bind to cells expressing surface immunoglobulin recognizing CD20 (alphaCD20), resulting in efficient transduction of target cells in a cognate antigen-dependent manner in vitro, and in vivo in a xenografted tumor model. Tumor suppression was observed in vivo, using the engineered lentivector to deliver a suicide gene to a xenografted tumor expressing alphaCD20. These results show the feasibility of engineering lentivectors to target immunoglobulin- specific cells to deliver a therapeutic effect. Such targeting lentivectors also could potentially be used to genetically mark antigen-specific B cells in vivo to study their B cell biology.

Gamma-retroviral vectors enveloped with an antibody and an engineered fusogenic protein achieved antigen-specific targeting.

Development of methods to engineer gamma-retroviral vectors capable of transducing target cells in a cell-specific manner could impact the future of the clinical application of gene therapy as well as the understanding of the biology of transfer gene vectors. Two molecular events are critical for controlling the entry of gamma-retroviral vectors to target cells: binding to cell-surface receptors and the subsequent fusion of viral vector membrane and cellular membrane. In this report, we evaluated a method to incorporate a membrane-bound antibody and a fusogenic molecule to provide binding and fusion functions respectively, into gamma-retroviral vectors for targeted gene delivery. An anti-CD20 antibody and a fusogenic protein derived from Sindbis virus glycoprotein could be efficiently co-displayed on the surface of viral vectors. Vectors bearing anti-CD20 antibody conferred their binding specificity to cells expressing CD20. Enhanced in vitro transduction towards CD20-expressing cells was observed for gamma-retroviral vectors displaying both an antibody and a fusogen. We found that the biological activity of the fusogen played an important role on the efficiency of such a targeting strategy and were able to engineer several mutant forms of the fusogen exhibiting elevated fusion function to improve the overall efficiency of targeted transduction. We devised an animal model to show that subcutaneous injection of such engineered vectors to the areas xenografted with target cells could achieve targeted gene delivery in vivo. Taken together, we demonstrated as proof-of-principle a flexible and modular two-molecule strategy for engineering targeting gamma-retroviral vectors.

Engineered lentivector targeting of dendritic cells for in vivo immunization.

We report a method of inducing antigen production in dendritic cells by in vivo targeting with lentiviral vectors that specifically bind to the dendritic cell-surface protein DC-SIGN. To target dendritic cells, we enveloped the lentivector with a viral glycoprotein from Sindbis virus engineered to be DC-SIGN-specific. In vitro, this lentivector specifically transduced dendritic cells and induced dendritic cell maturation. A high frequency (up to 12%) of ovalbumin (OVA)-specific CD8(+) T cells and a significant antibody response were observed 2 weeks after injection of a targeted lentiviral vector encoding an OVA transgene into naive mice. This approach also protected against the growth of OVA-expressing E.G7 tumors and induced regression of established tumors. Thus, lentiviral vectors targeting dendritic cells provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens.