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Tuesday, June 10

7:00 am – 6:00 pm Registration Open

7:30 am Breakfast Workshop (Sponsorships Available)

8:15 Chairperson’s Remarks
Eric Kmiec, Ph.D., Professor, Biology, University of Delaware/OrphageniX

8:20 A New Frontier in Gene Therapy
Eric Kmiec, Ph.D., Professor, Biology, University of Delaware/OrphageniX
Over the past seven years, we have pioneered the technique of gene repair wherein genetic mutations are corrected directly within context of the chromosome. This repair is facilitated by oligonucleotides , non-viral drug-like agents that does not induce an immune reaction or cause toxicity in humans. A number of genetic diseases including sickle cell anemia, spinal muscular atrophy and muscular dystrophy have been successfully treated in cell and animal models. Now, the focus is translating these results into a clinical trial.

8:50 Lasting Effects by Transient Gene Transfer: Epigenetics 
Casey Case, Ph.D., Vice President Research, SanBio Inc. 
Our cell therapy product is produced by transient transfection of Mesenchymal Stem Cells. The vector used encodes the Notch-1 IntraCellular Domain (NICD) a powerful regulator of devel-opmental cell fate. Transfection with this vector causes the cells to assume neuronal precursor-like properties and to lose the ability to differentiate down alternative paths. This beneficial effect persists long after the gene transfer vector is gone. We are exploring epigenetic mechanisms, such as CpG DNA methylation, to explain this phenomenon. These cells have shown beneficial results in models of stroke, Parkinson’s disease and spinal cord injury.

9:20 Sequence-Specific Modification of Genomic DNA by Oligonucleotides 
Dieter Gruenert, Ph.D., Professor, Senior Scientist, Cell Biology, California Pacific Medical Center Research Institute 
We have developed a strategy small fragment homologous replacement (SFHR) for modifying specific targets in the genomic DNA using small DNA fragments (SDF). Studies in hematopoie-tic stem cells, lymphoblasts, epithelial cells, and embryonic stem cells have shown SFHR-mediated modification. This approach has potential therapeutic applications as well as in the development of transgenic animals.

9:50 Networking Coffee Break, Poster and Exhibit Viewing

10:45 Nucleic Acid Delivery and Gene Repair in the Eye 
John M. Nickerson, Ph.D., Professor, Department of Ophthalmology, Emory University
Short single stranded oligonucleotides (ODNs) can be delivered into photoreceptor cells of the neural retina in vivo. We used a mouse strain bearing the retinal degeneration (rd1) lesion, a point mutation in a gene encoding the beta-subunit of cGMP phosphodiesterase (beta-PDE). Delivery of therapeutic ODNs to rd1 mouse eyes resulted in genomic DNA conversion from mutant to wild type sequence at a low but observable incidence. Correspondingly, observable beta-PDE immunoreactivity was detected. Rhodopsin immunopositive cells were detectable in the outer layers of the retina, suggesting that ODN-directed gene repair occurred in about 0.2% of cells. 

11:15 Selected Brief Poster Presentation

12:15 pm Close of Targeting Gene Therapy Conference 

12:30 Luncheon Technology Workshops (Sponsorships Available) or Lunch on Your Own

12:00 pm Registration Open 

2:00 Chairperson’s Remarks
Mark A. Kay M.D., Ph.D., Professor, Departments of Pediatrics and Genetics, Stanford University 

2:05 Systemic RNAi Therapeutics for Treating Infection
Mark A. Kay M.D., Ph.D., Professor, Departments of Pediatrics and Genetics, Stanford University 
Gene transfer vectors expressing shRNAs to target specific tissues have been utilized for treating different diseases. Recombinant AAV vectors expressing shRNAs have been shown to be effective in reducing hepatitis B viral replication in a transgenic mouse model. Interestingly, over expression of shRNAs can be toxic and even lethal because it interferes with normal mi-croRNA processing. The rate-limiting steps in mammalian tissues as well as effective strategies to maintain a high therapeutic index will be discussed.

2:35 Delivering RNAi Therapeutics
Muthiah Manoharan Ph.D., Vice President, Drug Discovery, Alnylam Pharmaceuticals

3:05 Delivery of Therapeutic RNA Interference into the GI tract
Johannes Fruehauf, M.D., Ph.D., Vice President, Research, Cequent Pharmaceuticals Inc.
Transkingdom RNA interference, (tkRNAi), uses nonpathogenic bacteria that are modified to act as manufacturers and carrier vehicles of interfering RNA against genes of interest. Activity has so far been shown across a wide range of targets. APCmin mice are a genetic model of human colon cancer. Here we show, that chronic oral treatment of APCmin mice (n=38) with tkRNAi bacteria resulted in a significant decrease of polyp formation through blockage of the CTNNB1 pathway in the gut. These findings open the possibility of developing RNAi-based drugs for organs and tissues outside of the areas targeted, including the gastrointestinal tract, genitourinary tract, and the skin.

3:35 Technology Spotlight (Sponsorships Available)

3:50 Networking Refreshment Break, Poster and Exhibit Viewing

4:30 Construction of phi29 DNA-Packaging Motor for Applications in Nanotechnology, Therapy, Diagnosis, and Drug Delivery
Peixuan Guo, Ph.D., Chair in Biomedical Engineering and Director of NIH Nanomedicine Development Center, University of Cincinnati 
Bacterial virus phi29 packaging RNA (pRNA) is an ATP-binding component of the DNA packaging motor. Its unique feature to form dimer, trimer, hexamer and patterned superstructures via the interaction of two interlocking loops makes it a promising tool in nanomedicine. Replacement or insertion of the 5’/3’helical domain with siRNA, ribozyme and receptor-binding aptamer does not interfere with the formation of the multimers, making it a novel vehicle for targeted therapy, pathogen detection and drug delivery. The chimeric siRNA/pRNA complex induced apoptosis in specific cancer cells, as tested in both cell culture and in animal trials. 

5:00 In vivo Imaging of siRNA Delivery and Silencing in Tumors
Anna Moore, Ph.D., Associate Professor, Department of Radiology and Director, Molecular Imaging Laboratory, Massachusetts General Hospital
The fast developing field of RNA interference requires monitoring of siRNA delivery to targeted organs and evaluating the efficiency of target gene silencing. Molecular imaging techniques represent a powerful tool for real-time non-invasive monitoring of various events at a near microscopic level and have superiour advantages over conventional in vitro and cell culture research techniques in biology. Therefore, molecular imaging approach fits perfectly to fulfill the need to monitor siRNA delivery and provides information in a fast, reproducible and non-invasive manner. This presentation will summarize the existing information on various imaging modalities and their application for siRNA imaging. 

5:30 Close of Day

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