scholarly journals Enhancers of Adeno-associated Virus AAV2 Transduction via High Throughput siRNA Screening

2011 ◽  
Vol 19 (6) ◽  
pp. 1152-1160 ◽  
Author(s):  
Alexis J Wallen ◽  
Gregory A Barker ◽  
David E Fein ◽  
Huiyan Jing ◽  
Scott L Diamond
Keyword(s):  
High Throughput ◽  
Adeno Associated Virus ◽  
Sirna Screening

scholarly journals High-Throughput Quantification of In Vivo Adeno-Associated Virus Transduction with Barcoded Non-Coding RNAs

2019 ◽  
Vol 30 (8) ◽  
pp. 946-956 ◽  
Author(s):  
Meiyu Xu ◽  
Jia Li ◽  
Jun Xie ◽  
Ran He ◽  
Qin Su ◽  
...  
Keyword(s):  
High Throughput ◽  
Adeno Associated Virus ◽  
Non Coding Rnas

scholarly journals Tracking Adeno-Associated Virus Capsid Evolution by High-Throughput Sequencing

2020 ◽  
Vol 31 (9-10) ◽  
pp. 553-564 ◽  
Author(s):  
Gustavo de Alencastro ◽  
Katja Pekrun ◽  
Paul Valdmanis ◽  
Matthew Tiffany ◽  
Jianpeng Xu ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Virus Capsid ◽  
Adeno Associated Virus

scholarly journals Identification and Validation of Small Molecules That Enhance Recombinant Adeno-associated Virus Transduction following High-Throughput Screens

2016 ◽  
Vol 90 (16) ◽  
pp. 7019-7031 ◽  
Author(s):  
Sarah C. Nicolson ◽  
Chengwen Li ◽  
Matthew L. Hirsch ◽  
Vincent Setola ◽  
R. Jude Samulski
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
High Throughput ◽  
Adeno Associated Virus ◽  
Virus Gene ◽  
Diploid Cells ◽  
High Throughput Screens ◽  
Group 1

ABSTRACTWhile the recent success of adeno-associated virus (AAV)-mediated gene therapy in clinical trials is promising, challenges still face the widespread applicability of recombinant AAV(rAAV). A major goal is to enhance the transduction efficiency of vectors in order to achieve therapeutic levels of gene expression at a vector dose that is below the immunological response threshold. In an attempt to identify novel compounds that enhance rAAV transduction, we performed two high-throughput screens comprising 2,396 compounds. We identified 13 compounds that were capable of enhancing transduction, of which 12 demonstrated vector-specific effects and 1 could also enhance vector-independent transgene expression. Many of these compounds had similar properties and could be categorized into five groups: epipodophyllotoxins (group 1), inducers of DNA damage (group 2), effectors of epigenetic modification (group 3), anthracyclines (group 4), and proteasome inhibitors (group 5). We optimized dosing for the identified compounds in several immortalized human cell lines as well as normal diploid cells. We found that the group 1 epipodophyllotoxins (teniposide and etoposide) consistently produced the greatest transduction enhancement. We also explored transduction enhancement among single-stranded, self-complementary, and fragment vectors and found that the compounds could impact fragmented rAAV2 transduction to an even greater extent than single-stranded vectors.In vivoanalysis of rAAV2 and all of the clinically relevant compounds revealed that, consistent with ourin vitroresults, teniposide exhibited the greatest level of transduction enhancement. Finally, we explored the capability of teniposide to enhance transduction of fragment vectorsin vivousing an AAV8 capsid that is known to exhibit robust liver tropism. Consistent with ourin vitroresults, teniposide coadministration greatly enhanced fragmented rAAV8 transduction at 48 h and 8 days. This study provides a foundation based on the rAAV small-molecule screen methodology, which is ideally used for more-diverse libraries of compounds that can be tested for potentiating rAAV transduction.IMPORTANCEThis study seeks to enhance the capability of adeno-associated viral vectors for therapeutic gene delivery applicable to the treatment of diverse diseases. To do this, a comprehensive panel of FDA-approved drugs were tested in human cells and in animal models to determine if they increased adeno-associated virus gene delivery. The results demonstrate that particular groups of drugs enhance adeno-associated virus gene delivery by unknown mechanisms. In particular, the enhancement of gene delivery was approximately 50 to 100 times better with than without teniposide, a compound that is also used as chemotherapy for cancer. Collectively, these results highlight the potential for FDA-approved drug enhancement of adeno-associated virus gene therapy, which could result in safe and effective treatments for diverse acquired or genetic diseases.

scholarly journals Targeting degradation pathways of RGS2 using high‐throughput siRNA screening

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Benita Sjogren ◽  
Steven Swaney ◽  
Richard Neubig
Keyword(s):  
High Throughput ◽  
Degradation Pathways ◽  
Sirna Screening

Identification and validation of vesicant therapeutic targets using a high-throughput siRNA screening approach

2014 ◽  
Vol 90 (2) ◽  
pp. 375-383
Author(s):  
Albert L. Ruff ◽  
Sarah Beach ◽  
John Lehman ◽  
Cristin Rothwell ◽  
James F. Dillman
Keyword(s):  
High Throughput ◽  
Therapeutic Targets ◽  
Screening Approach ◽  
Sirna Screening

scholarly journals Highly Divergent Integration Profile of Adeno-Associated Virus Serotype 5 Revealed by High-Throughput Sequencing

2013 ◽  
Vol 88 (5) ◽  
pp. 2481-2488 ◽  
Author(s):  
T. Janovitz ◽  
T. Oliveira ◽  
M. Sadelain ◽  
E. Falck-Pedersen ◽  
M. J. Imperiale
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
Serotype 5
Sign in / Sign up

Export Citation Format

Share Document