Receptor mediated gene transfer uses ligands that bind to cellular receptors to target and deliver DNA to specific tissues. It was first described by Cheng et al. who linked DNA to alpha-2 macroglobulin. Pioneering work by George and Catherine Wu developed the use of asialoglycoprotein receptor ligands to introduce genes into the liver. Other ligands used include galactosylated polylysine for the asialoglycoprotein receptor and transferrin for the transferrin receptor. Receptor mediated gene transfer allows specific delivery of genes to tissues and cell types but expression can be transient, requiring repeated injections.

1. RECEPTOR MEDIATED
GENE TRANSFER
ANKUSH
6681
MSc. BIOTECHNOLOGY
CENTRAL UNIVERSITY OF HARYANA

2. Receptor:
Definition
 A macromolecular component of the organism that binds the ligand
and initiates its effect.

4. INTRODUCTION
 Receptor mediated gene transfer is an attractive method
for therapeutically correcting human disease since it
permit the targeting of DNA to cellular receptor in specific
tissue of adult animal.
 Gene introduced by this technique have been shown to be
expressed in the target tissue for varying period .
 In this tech. the ability of receptor on the surface of a
variety of differentiated cell to efficiently bind and
internalize a ligand.

5.  The component used in receptor mediated gene transfer
system including the DNA of interest, a protein containing
the receptor targeting ligand , and a linking polycation.

6. History:
 Receptor mediated gene transfer was first describe by
Cheng et al.
 They linked a α-2 macroglobulin to DNA by covalent
modification.
 The first report of DNA transfer and gene expression via
receptor mediated endocytosis were made by the
pioneering work of George and Catherine Wu .
 They developed the method correctly used for the
introduction of gene into the liver via asialoglycoprotein
receptor.

7. Ligand used in receptor mediated gene
transfer:

8. ASIALOGLYCOPROTEIN RECEPTOR
 This approach in which functional genes are transferred into
hepatocytes in vitro and in vivo using a targeting ligand consisting of
galactosylated polylysine
 . The DNA enter through endocytosis by hepatocytes and result in the
uptake of DNA complexes by the hepatic asialoglycoprotein
 The asialoglycoprotein receptors are lectins which bind
asialoglycoprotein, glycoproteins from which a sialic acid has been
removed to expose galactose residues.
 .The asialoglycoprotein receptor has been demonstrated to have high
expression on the surface of hepatocytes and several human carcinoma
cell lines.

10. TRANSFERRIN RECEPTOR
 TfR-mediated endocytosis pathway showed that coupling of Tf to 350
nm or 50 nm latex minibead or to liposomes does not affect the
cellular uptake and biological activity of Tf in L1210 leukemia cells, rat
reticulo- cytes, or leukemic LzC cells.
 TF coated liposomes containing labeled DNA and partially internalized
by rabbit ery- throblasts after intravenous injection into rabbits.
 Similar liposomes coated with other ligands for cellular binding have
been successfully used for gene delivery and expression by other
groups.

12. ADVANTAGE OF RECEPTOR MEDIATED GENE
TRANSFER
 Relatively efficient in introducing DNA into host cell in
vitro and vivo.
 Specific delivery of exogenous gene to individual tissue
and cell type.
 Non infectious
 No size constrain of transgene.
 Can introduce different gene to same cell.
 Does not require cell replication for gene transfer and
expression.

13. DISADVANTAGES
 Relatively transient expression, need for repeated
injection.
 DNA ligand complex are difficult to prepare and little is
known about the structural feature of delivery vehicle.
 Incomplete understanding of the biological process
involved in the transfer and expression of the DNA into
host cell.
 Poorly immunogenic as compared to viral vector.

14. THANK YOU….