Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.

Abstract: Engineered mRNA useful in producing libraries of engineered mRNAs, polypeptide-engineered mRNA conjugates and diverse encoded polypeptide libraries, as well as novel ribozyes that join an mRNA to the translation product of the mRNA and methods of identifying members of diverse encoded polypeptide libraries which exhibit a desired activity. Also described are polypeptide-nucleic acid tag conjugates, methods of producing the conjugates and uses therefor.

Abstract: tRNA analogues which comprise a tRNA, such as tRNAphe; an amino acid moiety which acts as an acceptor substrate, but not as a donor substrate, for ribosome-directed peptidyl transfer and, thus, is stably linked to the acceptor stem of the tRNA; and a reactive or activatible moiety near or within the anticodon stem loop of the tRNA that can medidate the covalent coupling of the tRNA analogue to mRNA. Also described are polypeptide-tRNA analogue-mRNA fusions; libraries of encoded polypeptides; methods of producing and screening the libraries; and target members and their uses.

Abstract: tRNA analogues which comprise a tRNA, such as tRNAphe; an amino acid moiety which acts as an acceptor substrate, but not as a donor substrate, for ribosome-directed peptidyl transfer and, thus, is stably linked to the acceptor stem of the tRNA; and a reactive or activatible moiety near or within the anticodon stem loop of the tRNA that can medidate the covalent coupling of the tRNA analogue to mRNA. Also described are polypeptide-tRNA analogue-mRNA fusions; libraries of encoded polypeptides; methods of producing and screening the libraries; and target members and their uses.

Abstract: Engineered mRNA useful in producing libraries of engineered mRNAs, polypeptide-engineered mRNA conjugates and diverse encoded polypeptide libraries, as well as novel ribozymes that join an mRNA to the translation product of the mRNA and methods of identifying members of diverse encoded polypeptide libraries which exhibit a desired activity. Also described are polypeptide-nucleic acid tag conjugates, methods of producing the conjugates and uses therefor.

Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.

Abstract: tRNA analogues which comprise a tRNA, such as tRNAphe; an amino acid moiety which acts as an acceptor substrate, but not as a donor substrate, for ribosome-directed peptidyl transfer and, thus, is stably linked to the acceptor stem of the tRNA; and a reactive or activatible moiety near or within the anticodon stem loop of the tRNA that can medidate the covalent coupling of the tRNA analogue to mRNA. Also described are polypeptide-tRNA analogue-mRNA fusions; libraries of encoded polypeptides; methods of producing and screening the libraries; and target members and their uses.

Abstract: Engineered mRNA useful in producing libraries of engineered mRNAs, polypeptide-engineered mRNA conjugates and diverse encoded polypeptide libraries, as well as novel ribozymes that join an mRNA to the translation product of the mRNA and methods of identifying members of diverse encoded polypeptide libraries which exhibit a desired activity. Also described are polypeptide-nucleic acid tag conjugates, methods of producing the conjugates and uses therefor.