Use of rna trans-splicing for antibody gene transfer and...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/13 (2006.01) C07K 19/00 (2006.01) C12N 5/10 (2006.01) C12N 15/62 (2006.01) C12P 19/34 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2583306

The present invention provides methods and compositions for generating novel nucleic acid molecules through RNA trans-splicing that target a highly expressed pre-mRNA and contain the coding sequence for antibody polypeptide(s). The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with the target precursor messenger RNA molecule (target pre-mRNA) that is abundantly expressed or tumor specific and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecule (chimeric RNA) capable of encoding an antibody polypeptide. The invention provides for the in vivo production of chimeric RNA molecules that encode and result in the production of an antibody polypeptide that is therapeutically effective against, for example, infectious agents, cancer cells, transplantation antigens, rheumatoid arthritis, etc.

La présente invention concerne des méthodes et des compositions permettant de créer des nouvelles molécules d'acides nucléiques par un trans-épissage d'ARN qui cible un pré-ARNm fortement exprimé et renferme la séquence de codage pour un ou des polypeptides d'anticorps. Les compositions de l'invention contiennent des molécules de pré-trans-épissage conçues pour interagir avec la molécule précurseur cible d'ARN messager (pré-ARNm) qui est exprimée en abondance ou qui est spécifique de la tumeur, et induit une réaction de trans-épissage conduisant à la génération d'une nouvelle molécule chimère d'ARN capable de coder pour un polypeptide d'anticorps et renferment la séquence de codage pour le ou les polypeptides d'anticorps. L'invention concerne la production d'anticorpsin vivo de molécules chimères d'ARN qui codent pour un polypeptides d'anticorps et conduit à la production de ce dernier, lequel est thérapeutiquement efficace contre des agents infectieux, des cellules cancéreuses, des antigènes de transplantation et la polyarthrite rhumatoïde notamment.

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