Abstract:
The invention provides a fusion protein comprising an antigen binding domain linked to a bacteriophage decoration (Dec) protein along with a polynucleotide comprising the nucleic acid sequence of the fusion protein and a vector comprising the polynucleotide. Additionally, the invention provides a composition comprising the fusion protein and a virus-like particle (VLP), and a method of treating a disease in a mammal comprising administering a therapeutically effective amount of the composition to the mammal. The invention also provides a method of vaccinating against a disease comprising administering a composition comprising the fusion protein and a VLP encapsulating a protein.
Abstract:
The polynucleotide construct of (1) or (2) below is used to perform ribosome display, CIS display and/or mRNA display in order to screen a Fab against an antigen of interest: (1) a polynucleotide construct which monocistronically comprises a ribosome-binding sequence, Fab first chain-coding sequence, linker peptide-coding sequence, Fab second chain-coding sequence and scaffold-coding sequence in this order, and further comprises at its 3′-end a structure necessary for maintaining a complex with the Fab encoded by itself; and (2) a polynucleotide construct which comprises a Fab first chain-expressing cistron and a Fab second chain-expressing cistron each containing a ribosome-binding sequence, a Fab first chain-coding sequence or Fab second chain-coding sequence, and a scaffold-coding sequence in this order, the first Fab-expressing cistron further comprising at its 3′-end a ribosome stall sequence, said Fab second chain-expressing cistron further comprising at its 3′-end a structure necessary for maintaining a complex with the Fab encoded by itself.
Abstract:
The present invention provides methods for rapidly screening and measuring the ligand binding affinity of in vitro selected peptides to the cognate and off-target proteins. This general strategy is amenable to high throughput analysis because the peptides are synthesized by cell-free translation, as opposed to solid-phase synthesis required by traditional assays, and affinities can be readily measured in standard formats.
Abstract:
Fibronectin type III (10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative 10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes 10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are 10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.
Abstract:
The object of the present invention is to provide a fundamental therapy to mitochondrial genetic diseases caused by mutation of the mitochondrial (mt)DNA, and a pharmaceutical composition used for the same. The object can be solved by a polyamide compound binding to a target double-stranded mtDNA comprising A/T pair consisting of first A of the following sense-stranded DNA and the corresponding T, A/T pair consisting of 8th A of the following sense-stranded DNA and the corresponding T, G/C pair consisting of 9th G of the following sense-stranded DNA and the corresponding C, G/C pair consisting of 14th G of the following sense-stranded DNA and the corresponding C, T/A pair consisting of 15th T of the following sense-stranded DNA and the corresponding A, or the like, in the double-stranded DNA consisting of the sense-stranded DNA having base sequence of 5′-ATGGCAGAGCCCGGTAATCGCATAA-3′ (SEQ ID NO: 1) and the antisense-stranded DNA having base sequence of 5′-TTATGCGATTACCGGGCTCTGCCAT-3′ (SEQ ID NO: 2).
Abstract translation:本发明的目的是提供对由线粒体(mt)DNA的突变引起的线粒体遗传病的基础疗法和用于其的药物组合物。 该目的可以通过结合到包含由以下正义链DNA的第一个A组成的A / T对的对象双链mtDNA的聚酰胺化合物和由以下意义的第8位组成的对应的T,A / T对 并且相应的T,G / C对由以下正义链DNA的第9G组成的相应的C,G / C对由以下正义链DNA的第14位和对应的C,T / 由具有5'-ATGGCAGAGCCCGGTAATCGCATAA-3'(SEQ ID NO:3)的碱基序列的有义链DNA组成的双链DNA中的由第15位以下的正义链和相应的A等构成的对 :1)和具有5'-TTATGCGATTACCGGGCTCTGCCAT-3'(SEQ ID NO:2)的碱基序列的反义链DNA。
Abstract:
Fibronectin type III (10Fn3) binding domains having novel designs that are associated with reduced immunogenicity are provided. The application describes alternative 10Fn3 binding domains in which certain immunogenic regions are not modified when producing a binder in order to maintain recognition as a self antigen by the host organism. The application also describes 10Fn3 binding domains in which HLA anchor regions have been destroyed thereby reducing the immunogenic contribution of the adjoining region. Also provided are 10Fn3 domains having novel combinations of modified regions that can bind to a desired target with high affinity.
Abstract:
A method for screening a non-standard peptide compound in the peptide library that binds to the target substance, comprising the steps: (i) preparing a non-standard peptide library wherein a special (non-standard) amino acid is randomly incorporated into the peptide sequence by a cell-free (in vitro) translation system comprising a tRNA acylated by a special (non-standard) amino acid; (ii) bringing the obtained peptide library in contact with a target substance; and (iii) selecting a non-standard peptide that binds to the target substance as an active peptide.
Abstract:
A novel method for displaying proteins and peptides is disclosed in which individual proteins or peptides remain associated with the DNA encoding them. Proteins or peptides can be generated by in vitro translation of DNA templates, either free in solution or arrayed on a solid support, such that the proteins or peptides remain immobilized on their DNA templates. In particular, high throughput sequencing can be combined with high throughput functional characterization of encoded proteins and peptides, wherein the identity of each protein or peptide is determined by DNA sequencing, and functional studies are carried out directly on each protein or peptide while immobilized on the DNA template encoding it. The methods of the invention should find numerous applications, for example, in high throughput genetic or pharmacological screening, epitope mapping, and protein engineering and directed evolution.
Abstract:
The present invention relates to a nucleic acid linker for producing a complex of mRNA, and a protein or a peptide which is encoded by the mRNA, the linker comprising: a spacer portion at the 5′-terminal; a polynucleotide portion hybridizable with at least a part of a sequence of the mRNA; and an arm portion which has a connection portion for the protein or the peptide at the 3′-terminal, in which the spacer portion, the polynucleotide portion, and the arm portion form a single strand, and in which the polynucleotide portion contains a photoreactive base derivative.