Báo cáo y học: "Respirable antisense oligonucleotides: a new drug class for respiratory disease"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:"Respirable antisense oligonucleotides: a new drug class for respiratory disease. | Available online http content 2 1 005 Review Respirable antisense oligonucleotides a new drug class for respiratory disease Makoto Tanaka and Jonathan W Nyce Taisho Pharmaceutical Co. Tokyo Japan EpiGenesis Pharmaceuticals Princeton New Jersey USA Correspondence Jonathan W Nyce PhD EpiGenesis Pharmaceuticals Princeton NJ 08540-7007 USA. Tel 1 609 409 6080 fax 1 609 409 6126 e-mail jnyce@ Received 4 October 2000 Revisions requested 16 October 2000 Revisions received 10 November 2000 Accepted 10 November 2000 Published 18 December 2000 Respir Res 2001 2 5-9 2001 BioMed Central Ltd Print ISSN 1465-9921 Online ISSN 1465-993X Abstract Respirable antisense oligonucleotides RASONs which attenuate specific disease-associated mRNAs represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant and because of the markedly different target properties of mRNA and proteins they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However total insensitivity to nucleases is probably not an optimal design criterion for RASONs because moderate nuclease sensitivity can prevent their systemic delivery decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction inflammation and surfactant depletion in preclinical models of human asthma has a duration of effect of seven days and seems to undergo minimal systemic delivery. Keywords asthma DNA medicines respiratory disease Introduction Antisense oligonucleotides have been called the

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