Bruce Alan Sullenger

Journal article J Biol Chem · February 19, 2010 Featured Publication The interaction of factor Xa with factor Va on membranes to form prothrombinase profoundly increases the rate of the proteolytic conversion of prothrombin to thrombin. We present the characterization of an RNA aptamer (RNA(11F7t)) selected from a combinato ... Full text Link to item Cite

Notch promotes radioresistance of glioma stem cells.

Journal article Stem Cells · January 2010 Featured Publication Radiotherapy represents the most effective nonsurgical treatments for gliomas. However, gliomas are highly radioresistant and recurrence is nearly universal. Results from our laboratory and other groups suggest that cancer stem cells contribute to radiores ... Full text Link to item Cite

In vivo selection of tumor-targeting RNA motifs.

Journal article Nat Chem Biol · January 2010 Featured Publication In an effort to target the in vivo context of tumor-specific moieties, we screened a large library of nuclease-resistant RNA oligonucleotides in tumor-bearing mice to identify candidate molecules with the ability to localize to hepatic colon cancer metasta ... Full text Link to item Cite

Development of universal antidotes to control aptamer activity.

Journal article Nat Med · October 2009 Featured Publication With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, bu ... Full text Open Access Link to item Cite

Antimetastatic potential of PAI-1-specific RNA aptamers.

Journal article Oligonucleotides · June 2009 Featured Publication The serine protease inhibitor plasminogen activator inhibitor-1 (PAI-1) is increased in several cancers, including breast, where it is associated with a poor outcome. Metastatic breast cancer has a dismal prognosis, as evidenced by treatment goals that are ... Full text Link to item Cite

Crystal structure of an RNA aptamer bound to thrombin.

Journal article RNA · December 2008 Featured Publication Aptamers, an emerging class of therapeutics, are DNA or RNA molecules that are selected to bind molecular targets that range from small organic compounds to large proteins. All of the determined structures of aptamers in complex with small molecule targets ... Full text Link to item Cite

Assembling OX40 aptamers on a molecular scaffold to create a receptor-activating aptamer.

Journal article Chem Biol · July 21, 2008 Featured Publication We show that a molecular scaffold can be utilized to convert a receptor binding aptamer into a receptor agonist. Many receptors (including tumor necrosis receptor family members) are activated when they are multimerized on the cell surface. Molecular scaff ... Full text Link to item Cite

Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia.

Journal article Proc Natl Acad Sci U S A · August 7, 2007 Featured Publication Intimal hyperplasia (IH) and restenosis limit the long-term utility of bypass surgery and angioplasty due to pathological proliferation and migration of vascular smooth muscle cells (VSMCs) into the intima of treated vessels. Consequently, much attention h ... Full text Link to item Cite

Using 5'-PTMs to repair mutant beta-globin transcripts.

Journal article RNA · August 2007 Featured Publication Trans-splicing has been used to repair mutant RNA transcripts via competition for the spliceosome using pre-trans-splicing molecules, or "PTMs." Previous studies have demonstrated that functional PTMs can be designed for either 3'- or 5'-exon replacement, ... Full text Link to item Cite

A novel antidote-controlled anticoagulant reduces thrombin generation and inflammation and improves cardiac function in cardiopulmonary bypass surgery.

Journal article Mol Ther · September 2006 Featured Publication Heparin and protamine are the standard anticoagulant-antidote regimen used in almost every cardiopulmonary bypass (CPB) procedure even though both are associated with an array of complications and toxicities. Here we demonstrate that an anticoagulant aptam ... Full text Link to item Cite

Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras.

Journal article Nat Biotechnol · August 2006 Featured Publication Technologies that mediate targeted delivery of small interfering RNAs (siRNAs) are needed to improve their therapeutic efficacy and safety. Therefore, we have developed aptamer-siRNA chimeric RNAs capable of cell type-specific binding and delivery of funct ... Full text Link to item Cite

Retargeting mobile group II introns to repair mutant genes.

Journal article Mol Ther · May 2005 Featured Publication Retroposable elements such as retroviral and lentiviral vectors have been employed for many gene therapy applications. Unfortunately, such gene transfer vectors integrate genes into many different DNA sequences and unintended integration of the vector near ... Full text Link to item Cite

Aptamers: an emerging class of therapeutics.

Journal article Annu Rev Med · 2005 Featured Publication Numerous nucleic acid ligands, also termed decoys or aptamers, have been developed during the past 15 years that can inhibit the activity of many pathogenic proteins. Two of them, Macugen and E2F decoy, are in phase III clinical trials. Several properties ... Full text Link to item Cite

Antidote-mediated control of an anticoagulant aptamer in vivo.

Journal article Nat Biotechnol · November 2004 Featured Publication Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of ... Full text Link to item Cite

In vivo activity of nuclease-resistant siRNAs.

Journal article RNA · May 2004 Featured Publication Chemical modifications have been incorporated into short interfering RNAs (siRNAs) without reducing their ability to inhibit gene expression in mammalian cells grown in vitro. In this study, we begin to assess the potential utility of 2'-modified siRNAs in ... Full text Link to item Cite

Efficient and specific repair of sickle beta-globin RNA by trans-splicing ribozymes.

Journal article RNA · October 2003 Featured Publication Previously we demonstrated that a group I ribozyme can perform trans-splicing to repair sickle beta-globin transcripts upon transfection of in vitro transcribed ribozyme into mammalian cells. Here, we sought to develop expression cassettes that would yield ... Full text Link to item Cite

Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.

Journal article Proc Natl Acad Sci U S A · April 29, 2003 Featured Publication Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability. Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangi ... Full text Link to item Cite

Functional repair of a mutant chloride channel using a trans-splicing ribozyme.

Journal article J Clin Invest · December 2002 Featured Publication RNA repair has been proposed as a novel gene-based therapeutic strategy. Modified Tetrahymena group I intron ribozymes have been used to mediate trans-splicing of therapeutically relevant RNA transcripts, but the efficiency of the ribozyme-mediated RNA rep ... Full text Link to item Cite

RNA aptamers as reversible antagonists of coagulation factor IXa.

Journal article Nature · September 5, 2002 Featured Publication Many therapeutic agents are associated with adverse effects in patients. Anticoagulants can engender acute complications such as significant bleeding that increases patient morbidity and mortality. Antidote control provides the safest means to regulate dru ... Full text Link to item Cite

Emerging clinical applications of RNA.

Journal article Nature · July 11, 2002 Featured Publication RNA is a versatile biological macromolecule that is crucial in mobilizing and interpreting our genetic information. It is not surprising then that researchers have sought to exploit the inherent properties of RNAs so as to interfere with or repair dysfunct ... Full text Link to item Cite

Optimizing aptamer activity for gene therapy applications using expression cassette SELEX.

Journal article Mol Ther · July 2002 Featured Publication RNA aptamers against a variety of clinically relevant target proteins have been generated. For example, we previously isolated an RNA aptamer that inhibits the function of the E2F family of transcription factors that play a critical role in the control of ... Full text Link to item Cite

RNA repair: a novel approach to gene therapy.

Journal article Adv Drug Deliv Rev · November 15, 2000 Featured Publication Treatment of genetic disorders by gene therapy has conventionally been attempted through the transfer of a wild type version of a gene to the cells of a patient harboring defective copies of a disease associated gene. Despite significant advances using thi ... Full text Link to item Cite

Blocking the initiation of coagulation by RNA aptamers to factor VIIa.

Journal article Thromb Haemost · November 2000 Featured Publication The tissue factor/factor VIIa complex is thought to be the primary initiator of most physiologic blood coagulation events. Because of its proximal role in this process, we sought to generate new inhibitors of tissue factor/factor VIIa activity by targeting ... Link to item Cite

Series introduction: emerging clinical applications of nucleic acids.

Journal article J Clin Invest · October 2000 Featured Publication Full text Link to item Cite

Developing aptamers into therapeutics.

Journal article J Clin Invest · October 2000 Featured Publication Full text Link to item Cite

Enhancing RNA repair efficiency by combining trans-splicing ribozymes that recognize different accessible sites on a target RNA.

Journal article Mol Ther · September 2000 Featured Publication Recent reports have demonstrated that trans-splicing ribozymes can be employed to repair mutant RNAs. One key factor that influences RNA repair efficiency is the accessibility of the substrate RNA for ribozyme binding, which is complicated by the fact that ... Full text Link to item Cite

Induction of wild-type p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts.

Journal article Proc Natl Acad Sci U S A · July 18, 2000 Featured Publication Several groups have attempted to develop gene therapy strategies to treat cancer via introduction of the wild-type (wt) p53 cDNA into cancer cells. Unfortunately, these approaches do not result in regulated expression of the p53 gene and do not reduce expr ... Full text Link to item Cite

Evaluating group I intron catalytic efficiency in mammalian cells.

Journal article Mol Cell Biol · October 1999 Featured Publication Recent reports have demonstrated that the group I ribozyme from Tetrahymena thermophila can perform trans-splicing reactions to repair mutant RNAs. For therapeutic use, such ribozymes must function efficiently when transcribed from genes delivered to human ... Full text Link to item Cite

RNA repair as a novel approach to genetic therapy.

Journal article Gene Ther · April 1999 Featured Publication Full text Link to item Cite

Optimizing the substrate specificity of a group I intron ribozyme.

Journal article Biochemistry · March 16, 1999 Featured Publication Group I ribozymes can repair mutant RNAs via trans-splicing. Unfortunately, substrate specificity is quite low for the trans-splicing reaction catalyzed by the group I ribozyme from Tetrahymenathermophila. We have used a systematic approach based on bioche ... Full text Link to item Cite

Probing the interplay between the two steps of group I intron splicing: competition of exogenous guanosine with omega G.

Journal article Biochemistry · December 22, 1998 Featured Publication One largely unexplored question about group I intron splicing is how the cleavage and ligation steps of the reaction are coordinated. We describe a simple in vitro trans-splicing model system in which both steps take place, including the exchange of ligand ... Full text Link to item Cite

Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors.

Journal article Science · June 5, 1998 Featured Publication Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene ther ... Full text Link to item Cite

Evaluating and enhancing ribozyme reaction efficiency in mammalian cells.

Journal article Nat Biotechnol · September 1997 Featured Publication The ability of ribozymes to cleave specific transcripts and repair defective RNAs in the test tube has engendered speculation about their potential clinical utility. Therapeutic development has been hindered by an inability to evaluate and optimize the eff ... Full text Link to item Cite

Trans-splicing reactions by ribozymes.

Journal article Methods Mol Biol · 1997 Featured Publication Full text Link to item Cite

Isolation of a nuclease-resistant decoy RNA that can protect human acetylcholine receptors from myasthenic antibodies.

Journal article Nat Biotechnol · January 1997 Featured Publication The muscular weakness and fatigability associated with myasthenia gravis are engendered by autoantibodies directed against acetylcholine receptors on muscle cells at neuromuscular junctions. The pathogenic consequences of this immune response can potential ... Full text Link to item Cite

Inhibition of cell proliferation by an RNA ligand that selectively blocks E2F function.

Journal article Nat Med · December 1996 Featured Publication The control of cell proliferation is of central importance to the proper development of a multicellular organism, the homeostatic maintenance of tissues, and the ability of certain cell types to respond appropriately to environmental cues. Disruption of no ... Full text Link to item Cite

Ribozyme-mediated repair of RNAs encoding mutant tumor suppressors.

Journal article Cytokines Mol Ther · September 1996 Featured Publication The observation that a number of genetic mutations can result in neoplastic transformation has led many investigators to speculate that gene therapy may represent a useful approach to treat cancer. Conceptually, this application of gene therapy seems quite ... Link to item Cite

Isolation of a nuclease-resistant decoy RNA that selectively blocks autoantibody binding to insulin receptors on human lymphocytes.

Journal article J Exp Med · August 1, 1996 Featured Publication An RNA containing 2'-amino pyrimidines has been isolated using in vitro selection techniques that specifically and avidly (apparent Kd approximately 30 nM) binds a mouse monoclonal antibody called MA20. This 2'-amino-derivatized RNA is at least 10,000-fold ... Full text Link to item Cite

Tagging ribozyme reaction sites to follow trans-splicing in mammalian cells.

Journal article Nat Med · June 1996 Featured Publication In mammalian cells, genetic instructions are usually revised by RNA splicing before they are translated to proteins. Here we demonstrate that a trans-splicing group I ribozyme can be employed to intentionally modify the sequence of targeted transcripts in ... Full text Link to item Cite

Revising messages traveling along the cellular information superhighway.

Journal article Chem Biol · May 1995 Featured Publication Cells use RNA messages to carry instructions from the genome to ribosomes about the types of proteins that should be made. These messages are generally revised by splicing before translation. Engineering ribozymes that can use splicing to repair mutant tra ... Full text Link to item Cite

Selection of an RNA molecule that mimics a major autoantigenic epitope of human insulin receptor.

Journal article Proc Natl Acad Sci U S A · March 14, 1995 Featured Publication Autoimmunity often involves the abnormal targeting of self-antigens by antibodies, leading to tissue destruction and other pathologies. This process could potentially be disrupted by small ligands that bind specifically to autoantibodies and inhibit their ... Full text Link to item Cite

Colocalizing ribozymes with substrate RNAs to increase their efficacy as gene inhibitors.

Journal article Appl Biochem Biotechnol · 1995 Featured Publication The ability to target ribozymes to specifically cleave viral RNAs in vitro has led to much speculation about their potential therapeutic value as antiviral agents in vivo. To transfer a ribozyme's potential as an antiviral agent from test tubes to cells an ... Full text Link to item Cite

AIDS and HIV infection.

Journal article Mol Cell Biol Hum Dis Ser · 1995 Featured Publication Full text Link to item Cite

Alternative approaches for the application of ribozymes as gene therapies for retroviral infections.

Journal article Adv Pharmacol · 1995 Featured Publication Full text Link to item Cite

Ribozyme-mediated repair of defective mRNA by targeted, trans-splicing.

Journal article Nature · October 13, 1994 Featured Publication Ribozymes can be targeted to cleave specific RNAs, which has led to much interest in their potential as gene inhibitors. Such trans-cleaving ribozymes join a growing list of agents that stop the flow of genetic information. Here we describe a different app ... Full text Link to item Cite

Tethering ribozymes to a retroviral packaging signal for destruction of viral RNA.

Journal article Science · December 3, 1993 Featured Publication Cellular compartmentalization of RNAs is thought to influence their susceptibility to ribozyme cleavage. As a test of this idea, two retroviral vectors--one encoding a hammer-head ribozyme designed to cleave lacZ transcripts and another encoding the lacZ m ... Full text Link to item Cite

Overexpression of RRE-derived sequences inhibits HIV-1 replication in CEM cells.

Journal article New Biol · January 1992 Featured Publication Overexpression of sequences corresponding to the major Rev-binding site in the Rev response element of human immunodeficiency virus type 1 (HIV-1) (RRE decoys) was used to render cells resistant to HIV-1 replication. This was accomplished by the use of a c ... Link to item Cite

Analysis of trans-acting response decoy RNA-mediated inhibition of human immunodeficiency virus type 1 transactivation.

Journal article J Virol · December 1991 Featured Publication Overexpression of trans-acting response element (TAR)-containing sequences (TAR decoys) in CEM SS cells renders cells resistant to human immunodeficiency type 1 (HIV-1) replication. Mutagenesis of TAR was used to investigate the molecular mechanism underly ... Full text Link to item Cite

Expression of chimeric tRNA-driven antisense transcripts renders NIH 3T3 cells highly resistant to Moloney murine leukemia virus replication.

Journal article Mol Cell Biol · December 1990 Featured Publication NIH 3T3 cells infected with Moloney murine leukemia virus (MoMLV) express high levels of virus-specific RNA. To inhibit replication of the virus, we stably introduced chimeric tRNA genes encoding antisense templates into NIH 3T3 cells via a retroviral vect ... Full text Link to item Cite

Overexpression of TAR sequences renders cells resistant to human immunodeficiency virus replication.

Journal article Cell · November 2, 1990 Featured Publication Overexpression of TAR-containing sequences (TAR decoys) was used to render cells resistant to HIV replication. A chimeric tRNA(meti)-TAR transcription unit contained in a double copy murine retroviral vector was used to express high levels of HIV-1 TAR-con ... Full text Link to item Cite

Improved gene expression upon transfer of the adenosine deaminase minigene outside the transcriptional unit of a retroviral vector.

Journal article Proc Natl Acad Sci U S A · May 1989 Featured Publication This study describes a type of retroviral vector called double-copy (DC) vector that was designed to improve the expression of transduced genes. The unique feature of DC vectors is that the transduced gene is inserted within the U3 region of the 3' long te ... Full text Link to item Cite