AAV Vectors Pseudotyped with Capsids from Porcine and Bovine Species Mediate In Vitro and In Vivo Gene Delivery.

Adeno-associated virus (AAV) vectors are among the most widely used delivery vehicles for in vivo gene therapy as they mediate robust and sustained transgene expression with limited toxicity. However, a significant impediment to the broad clinical success of AAV-based therapies is the widespread presence of pre-existing humoral immunity to AAVs in the human population. This immunity arises from the circulation of non-pathogenic endemic human AAV serotypes. One possible solution is to use non-human AAV capsids to pseudotype transgene-containing AAV vector genomes of interest. Due to the low probability of human exposure to animal AAVs, pre-existing immunity to animal-derived AAV capsids should be low. Here, we characterize two novel AAV capsid sequences: one derived from porcine colon tissue and the other from a caprine adenovirus stock. Both AAV capsids proved to be effective transducers of HeLa and HEK293T cells in vitro. In vivo, both capsids were able to transduce the murine nose, lung, and liver after either intranasal or intraperitoneal administration. In addition, we demonstrate that the porcine AAV capsid likely arose from multiple recombination events involving human- and animal-derived AAV sequences. We hypothesize that recurrent recombination events with similar and distantly related AAV sequences represent an effective mechanism for enhancing the fitness of wildtype AAV populations.

Beyond BMI: a feasibility study implementing NutriSTEP in primary care practices using electronic medical records (EMRs). / Au-delà de l'IMC : étude de faisabilité de la mise en oeuvre de NutriSTEP dans les établissements de soins primaires au moyen des dossiers médicaux électroniques (DME).

INTRODUCTION: Primary care providers have a role to play in supporting the development of healthy eating habits, particularly in a child's early years. This study examined the feasibility of implementing the NutriSTEP® screen-a 17-item nutrition risk screening tool validated for use with both toddler and preschooler populations-integrated with an electronic medical record (EMR) in primary care practices in Ontario, Canada, to inform primary care decision-making and public health surveillance. METHODS: Five primary care practices implemented the NutriSTEP screen as a standardized form into their EMRs. To understand practitioners' experiences with delivery and assess factors associated with successful implementation, we conducted semi-structured qualitative interviews with primary care providers who were most knowledgeable about NutriSTEP implementation at their site. We assessed the quality of the extracted patient EMR data by determining the number of fully completed NutriSTEP screens and documented growth measurements of children. RESULTS: Primary care practices implemented the NutriSTEP screen as part of a variety of routine clinical contacts; specific data collection processes varied by site. Valid NutriSTEP screen data were captured in the EMRs of 80% of primary care practices. Approximately 90% of records had valid NutriSTEP screen completions and 70% of records had both valid NutriSTEP screen completions and valid growth measurements. CONCLUSION: Integration of NutriSTEP as a standardized EMR form is feasible in primary care practices, although implementation varied in our study. The application of EMR-integrated NutriSTEP screening as part of a comprehensive childhood healthy weights surveillance system warrants further exploration.