Recombinant human adenovirus serotype 5 (Ad5/35F-IL2) with
modified fibres containing the C-terminal domain fiber-knob of human adenovirus
serotype 35, carrying the gene of recombinant human IL-2, has been designed. As a
result of the fiber modification, the adenovirus can efficiently deliver the genetic
information to bone marrow leukocytes and the tumor blood cells KG-1A (human
myeloblastic leukemia cells) and U937 (human histiocytic lymphoma cells), which are
normally resistant to Ad5 infection. The flow cytometry data reveal that the
modified Ad5/35F penetrates into a population of monocytes, granulocytes, and blast
cells of human bone marrow. The expression of interleukin-2 in CAR-negative bone
marrow leukocytes (3682.52 ± 134.21 pg/ml) and the cell lines KG-1A (748.3 ± 32.8
pg/ml) and U937 (421.5 ± 59.4 pg/ml) transduced with adenovirus Ad5/35F-IL2 is
demonstrated. The fiber-modified adenovirus can be used as a vector for the
efficient gene delivery of interleukin-2 to human normal and tumor hematopoietic
cells.
Current targeting strategies for genetic vectors imply the creation of a
specific vector for every targeted receptor, which is time-consuming and
expensive. Therefore, the development of a universal vector system whose
surface can specifically bind molecules to provide efficient targeting is of
particular interest. In this study, we propose a new approach in creating
targeted vectors based on the genome of human adenovirus serotype 5 carrying
the modified gene of the capsid protein pIX (Ad5-EGFP-pIX-ER): recombinant
pseudoadenoviral nanoparticles (RPANs). The surfaces of such RPANs are able to
bind properly modified chimeric nanoantibodies that specifically recognize a
particular target antigen (carcinoembryonic antigen (CEA)) with high affinity.
The efficient binding of nanoantibodies (aCEA-RE) to the RPAN capsid surfaces
has been demonstrated by ELISA. The ability of the constructed vector to
deliver target genes has been confirmed by experiments with the tumor cell
lines A549 and Lim1215 expressing CEA. It has been shown that Ad5-EGFP-pIX-ER
carrying aCEA-RE on its surface penetrates into the tumor cell lines A549 and
Lim1215 via the CAR-independent pathway three times more efficiently than
unmodified RPAN and Ad5-EGFP-pIX-ER without nanoantibodies on the capsid
surface. Thus, RPAN Ad5-EGFP-pIX-ER is a universal platform that may be useful
for targeted gene delivery in specific cells due to
“nanoantibody–modified RPAN” binding.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.