Theoretical and experimental approaches to design effective antisense oligonucleotides.

Among the large number of possible antisense oligonucleotides (asODN) against a given target nucleic acid, only a small number of species seems to give rise to satisfactorily strong inhibition of target gene expression in living cells. Therefore much attention is paid to strategies that help to successfully design effective asODN. Here, selected experimental approaches and theoretical concepts will be briefly described that have been developed to increase the probability of success in the use of asODN. Advantages and disadvantages of these strategies will be compared and the relatively new and controversially discussed concept of a theoretical and computer-supported design of effective asODN will be addressed.

[1]  J. Devereux,et al.  A comprehensive set of sequence analysis programs for the VAX , 1984, Nucleic Acids Res..

[2]  J. F. Atkins,et al.  A rapid in vitro method for obtaining RNA accessibility patterns for complementary DNA probes: correlation with an intracellular pattern and known RNA structures. , 1997, Nucleic acids research.

[3]  S. Grabley,et al.  Inhibition of viral growth by antisense oligonucleotides directed against the IE110 and the UL30 mRNA of herpes simplex virus type-1. , 1995, Biological chemistry Hoppe-Seyler.

[4]  V. Patzel,et al.  Theoretical and Experimental Selection Parameters for HBV-Directed Antisense RNA Are Related to Increased RNA-RNA Annealing , 1997, Biological chemistry.

[5]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[6]  O Ritter,et al.  X-HUSAR, an X-based graphical interface for the analysis of genomic sequences. , 1995, Computer methods and programs in biomedicine.

[7]  P. Romby,et al.  Implications of RNA structure on the annealing of a potent antisense RNA directed against the human immunodeficiency virus type 1. , 1997, Biochemistry.

[8]  W D Wilson,et al.  Sequence specific thermodynamic and structural properties for DNA.RNA duplexes. , 1994, Biochemistry.

[9]  G. Sczakiel,et al.  Kinetic selection of HPV 16 E6/E7-directed antisense nucleic acids: anti-proliferative effects on HPV 16-transformed cells. , 1999, Nucleic acids research.

[10]  S. Crooke,et al.  Properties of Cloned and Expressed Human RNase H1* , 1999, The Journal of Biological Chemistry.

[11]  E. Southern,et al.  Analyzing and comparing nucleic acid sequences by hybridization to arrays of oligonucleotides: evaluation using experimental models. , 1992, Genomics.

[12]  J. Rossi,et al.  Rapid determination and quantitation of the accessibility to native RNAs by antisense oligodeoxynucleotides in murine cell extracts. , 1998, Nucleic acids research.

[13]  P. Schwille,et al.  Quantitative hybridization kinetics of DNA probes to RNA in solution followed by diffusional fluorescence correlation analysis. , 1996, Biochemistry.

[14]  E. Southern,et al.  Selecting effective antisense reagents on combinatorial oligonucleotide arrays , 1997, Nature Biotechnology.

[15]  K U Mir,et al.  Arrays of complementary oligonucleotides for analysing the hybridisation behaviour of nucleic acids. , 1994, Nucleic acids research.

[16]  G Sczakiel,et al.  Computer-aided calculation of the local folding potential of target RNA and its use for ribozyme design. , 1997, Methods in molecular biology.

[17]  M. Strauss,et al.  Selection of efficient cleavage sites in target RNAs by using a ribozyme expression library , 1995, Molecular and cellular biology.

[18]  Denman Rb,et al.  Using RNAFOLD to predict the activity of small catalytic RNAs. , 1993 .

[19]  G Sczakiel,et al.  Computer-aided search for effective antisense RNA target sequences of the human immunodeficiency virus type 1. , 1993, Antisense research and development.

[20]  G Sczakiel,et al.  A theoretical approach to select effective antisense oligodeoxyribonucleotides at high statistical probability. , 1999, Nucleic acids research.

[21]  W. James,et al.  Computational approaches to the identification of ribozyme target sites. , 1997, Methods in molecular biology.

[22]  R. Hanecak,et al.  Combinatorial Screening and Rational Optimization for Hybridization to Folded Hepatitis C Virus RNA of Oligonucleotides with Biological Antisense Activity* , 1997, The Journal of Biological Chemistry.

[23]  Randall R. Sakai,et al.  Mapping of RNA accessible sites for antisense experiments with oligonucleotide libraries , 1998, Nature Biotechnology.

[24]  G. Sczakiel,et al.  In vitro selection of fast-hybridizing and effective antisense RNAs directed against the human immunodeficiency virus type 1. , 1993, Nucleic acids research.

[25]  Yedy Israel,et al.  Tetranucleotide GGGA Motif in Primary RNA Transcripts , 1998, The Journal of Biological Chemistry.

[26]  Doriano Fabbro,et al.  Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase , 1996, Nature Medicine.

[27]  H. Soreq,et al.  Probing accessible sites for ribozymes on human acetylcholinesterase RNA. , 1997, RNA.

[28]  G. Sczakiel,et al.  Mechanistic insights into p53-promoted RNA-RNA annealing. , 1997, Journal of molecular biology.

[29]  M. Tommasino,et al.  Oncogenes and antioncogenes in the development of HPV associated tumors. , 1997, Clinics in dermatology.

[30]  G. Trainor,et al.  Potent antisense oligonucleotides to the human multidrug resistance-1 mRNA are rationally selected by mapping RNA-accessible sites with oligonucleotide libraries. , 1996, Nucleic acids research.

[31]  G. Sczakiel,et al.  Kinetic selectivity of complementary nucleic acids: bcr-abl-directed antisense RNA and ribozymes. , 1996, Journal of molecular biology.