2001 Fiscal Year Final Research Report Summary
In vivo gene therapy utilising transferrin receptor-operated transfer
| Project/Area Number |
12835004
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
SHICHIRI Masayoshi Tokyo Medical and Dental University, Department of Clinical and Molecular Endocrinology, Lecturer, 医学部・附属病院, 講師 (10206097)
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| Project Period (FY) |
2000 – 2001
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| Keywords | gene therapy / LDL receptor deficiency / balloon-injured rat / transferrin receptor / max gene / Light Cycler |
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| Research Abstract |
Cationic liposome DNA complex (CLDC) intravenous gene delivery has been shown to direct gene expression to vascular endothelial cells, monocytes, and macrophages. CLDC gene delivery avoids immune system reactions associated with viral vectors, yet the low efficiency of gene delivery using CLDC has limited the use of non-viral vectors for gene therapy. Ligand-facilitated transfer of CLDC has been shown to markedly increase in vitro gene delivery efficiency, but has not increased in vivo efficiency to the magnitude of adenoviral vectors and has remained unsuccessful in applications to systemic gene therapy. Introduction of ligands such as transferrin and asialofetuin into a CLDC has been reported to generate in vivo expression of reporter plasmids while others report low transfer efficiency. We have demonstrated that a combination of CLDC-transferrin enhanced intravenous delivery in circulating leukocytes. Transferrin-facilitated intravenous delivery of cationic liposome CDNA complexes could serve as an important adjunct therapy for the treatment of disorders, especially those in which deficiency of a single gene can be replaced by transfer of an exogenous gene into circulating cells.
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