Peri-Implantation Targeting Using Modified Adenoviral Vectors

The aim was to conduct a comparative morphological analysis of the effect of implantation and modified adenovirus Ad 5/3 on the efficiency of local gene delivery to cells of the peri-implantation niche in vivo. Material and methods. The experiments were carried out on laboratory rats, which were implanted with collagen membranes for a period of 2 weeks. Three and seven days after the introduction of adenoviruses (wt, Ad 5/3), the tissues were fixed for histological examination and analysis of transduced cells by in situ PCR. Results. The results showed that the presence of a collagen implant improved the biodistribution of viral particles, and the modification of Ad 5/3 significantly increased the efficiency of transduction of fibroblasts and macrophages in the peri-implantation zone. In the absence of an implant, the transduction efficiency decreased for both types of adenoviruses. Morphometric analysis revealed that the main transduced cells were fibroblasts of the connective tissue capsule surrounding the implant. Conclusion. Based on comparative morphological and molecular biological studies, an optimal protocol for local gene delivery using adenoviral vectors for peri-implantation targeting was determined. The effect of adenovirus modification on the tropism and efficiency of gene delivery to the cellular components of the PIN was characterized, and it was found that Ad 5/3 significantly exceeds AD wt in these parameters. The development and further application of the peri-implantation targeting method proposed by us can ensure local, effective and safe gene delivery, which will significantly expand the indications for gene therapy and its availability to doctors and patients. In addition, this method can be adapted for use in various organs and for various diseases.

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