Chris Black - Academia.edu (original) (raw)

Papers by Chris Black

Research paper thumbnail of Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-( N Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′- O ,4′- C -Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

Journal of Medicinal Chemistry, 2010

To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we h... more To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having N-O bonds. These modifications include N-MeO-amino BNA, N-Me-aminooxy BNA, 2 0 ,4 0 -BNA NC [NMe], and 2 0 ,4 0 -BNA NC bridged nucleoside analogues. These modifications provided increased thermal stability and improved in vitro activity compared to the corresponding ASO containing the MOE modification. Additionally, ASOs containing N-MeO-amino BNA, N-Me-aminooxy BNA, and 2 0 ,4 0 -BNA NC [NMe] modifications showed improved in vivo activity (>5-fold) compared to MOE ASO. Importantly, toxicity parameters, such as AST, ALT, liver, kidney, and body weights, were found to be normal for N-MeO-amino BNA, N-Me-aminooxy BNA, and 2 0 ,4 0 -BNA NC [NMe] ASO treated animals. The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2 0 ,4 0 -BNA NC [NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts.

Research paper thumbnail of Interoperability Problems Caused by Transitioning to a Service Oriented Environment

A major Department of Defense challenge continues to be the synchronized interoperability of mult... more A major Department of Defense challenge continues to be the synchronized interoperability of multiple command and control and M&S programs. The Army has three major Command and Control (C2) efforts to contend with: ABCS migratio n, FCS development, and the Joint Net Enabled Command and Control (NECC) program. These C2 systems will be operating in a Service Oriented Environment (SOE)

Research paper thumbnail of Antisense Oligonucleotides Containing Conformationally Constrained 2′,4′-( N Methoxy)aminomethylene and 2′,4′-Aminooxymethylene and 2′- O ,4′- C -Aminomethylene Bridged Nucleoside Analogues Show Improved Potency in Animal Models

Journal of Medicinal Chemistry, 2010

To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we h... more To identify chemistries and strategies to improve the potency of MOE second generation ASOs, we have evaluated gapmer antisense oligonucleotides containing BNAs having N-O bonds. These modifications include N-MeO-amino BNA, N-Me-aminooxy BNA, 2 0 ,4 0 -BNA NC [NMe], and 2 0 ,4 0 -BNA NC bridged nucleoside analogues. These modifications provided increased thermal stability and improved in vitro activity compared to the corresponding ASO containing the MOE modification. Additionally, ASOs containing N-MeO-amino BNA, N-Me-aminooxy BNA, and 2 0 ,4 0 -BNA NC [NMe] modifications showed improved in vivo activity (>5-fold) compared to MOE ASO. Importantly, toxicity parameters, such as AST, ALT, liver, kidney, and body weights, were found to be normal for N-MeO-amino BNA, N-Me-aminooxy BNA, and 2 0 ,4 0 -BNA NC [NMe] ASO treated animals. The data generated in these experiments suggest that N-MeO-amino BNA, N-Me-aminooxy BNA, and 2 0 ,4 0 -BNA NC [NMe] are useful modifications for applications in both antisense and other oligonucleotide based drug discovery efforts.

Research paper thumbnail of Interoperability Problems Caused by Transitioning to a Service Oriented Environment

A major Department of Defense challenge continues to be the synchronized interoperability of mult... more A major Department of Defense challenge continues to be the synchronized interoperability of multiple command and control and M&S programs. The Army has three major Command and Control (C2) efforts to contend with: ABCS migratio n, FCS development, and the Joint Net Enabled Command and Control (NECC) program. These C2 systems will be operating in a Service Oriented Environment (SOE)