scholarly journals mRNA Leapfrogs DNA to Show Promise for Therapeutic Gene Transfer

2012 ◽  
Vol 20 (4) ◽  
pp. 694-695 ◽  
Author(s):  
Eli Gilboa
Keyword(s):  
Gene Transfer ◽  
Therapeutic Gene

scholarly journals DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer

2008 ◽  
Vol 36 (9) ◽  
pp. e49-e49 ◽  
Author(s):  
Gary P. Wang ◽  
Alexandrine Garrigue ◽  
Angela Ciuffi ◽  
Keshet Ronen ◽  
Jeremy Leipzig ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Adverse Events ◽  
Therapeutic Gene ◽  
Dna Bar Coding

Dual-expressing adenoviral vectors encoding the sodium iodide symporter for use in noninvasive radiological imaging of therapeutic gene transfer

2006 ◽  
Vol 33 (3) ◽  
pp. 391-398 ◽  
Author(s):  
Gang Niu ◽  
Richard D. Anderson ◽  
Mark T. Madsen ◽  
Michael M. Graham ◽  
Larry W. Oberley ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Sodium Iodide ◽  
Adenoviral Vectors ◽  
Radiological Imaging ◽  
Sodium Iodide Symporter ◽  
Therapeutic Gene

Directed Evolution of Immune-Escaping Adeno-Associated Virus Vectors

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3532-3532
Author(s):  
Stephan Maersch ◽  
Anke Huber ◽  
Michael Hallek ◽  
Hildegard Buening ◽  
Luca Perabo
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Gene Transfer ◽  
Directed Evolution ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Multiple Point ◽  
Repeated Treatment ◽  
Therapeutic Gene ◽  
Adeno Associated Virus

Abstract Efficiency of therapeutic gene transfer by adeno-associated virus of serotype 2 (AAV-2) vectors is hampered in patients with pre-existing immunity against the natural virus. Genetic engineering by rational design or directed evolution has been employed in the last 3 years to generate capsids that escape antibody neutralization and has led to identify several amino acid residues of the capsid proteins that can be mutated in order to decrease antibody recognition (Perabo et al., 2006; Maheshri et al, 2006; Lochrie et al., 2006). In this novel study, we aimed to exploit the comprehensive knowledge gathered so far by generating novel capsid variants that carried multiple point mutations at these previously identified sites. Capsid libraries were generated by codon randomization of several immunogenic residues and screened to isolate mutants that most efficiently infected human cells despite the presence of anti-AAV2 neutralizing antibodies. Besides testing novel combinations of concomitant mutations at these sites, this approach allowed for the first time an exhaustive scanning of combinations of all 20 natural amino acids at each position. We identified several novel capsid mutants that remain highly infectious even when incubated with serum concentrations that completely neutralize wild type AAV2. Our results demonstrate that combining mutations at several sites it is possible to improve the immune-escaping ability of the capsid. In addition, we show that escaping ability and other biological characteristics of these mutants are strongly dependent on the type of amino acid substituted, demonstrating that an exact choice of substituted amino acids is essential to maximize stealth properties and minimize loss of packaging ability, particle stability and transduction efficacy. These vectors can be used for therapeutic gene transfer to patients with pre-existing immunity, or for repeated treatment after antibodies are generated upon first application.

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