A summary of the published data on host plants and morphology of immature stages of Australian jewel beetles (Coleoptera: Buprestidae) : with additional new records

A summary is given of the published host plant and descriptive immature stage morphology data for 671 species and 11 subspecies in 54 genera of Australian jewel beetles (Coleoptera: Buprestidae). New host data for 155 species and 3 subspecies in 17 genera including the first published data for 75 species are included

Adeno-associated virus serotype 9-mediated pulmonary transgene expression: effect of mouse strain, animal gender and lung inflammation.

Gene therapy holds great potential for the treatment of various acquired and inherited pulmonary diseases. Among various viral vectors, adeno-associated viral (AAV) vectors have been most frequently used in different clinical trials of pulmonary gene therapy. In the present study, we examined the kinetics and duration of transgene expression, vector biodistribution and development of neutralizing antibodies (NAB) in mice after pulmonary application of AAV2/9 vector. The pulmonary route of application did not affect any of the measured parameters. Transgene expression and biodistribution analysis at day 450 post-application confirmed the systemic spread of the vector after pulmonary delivery. Using SPB(-/-) mice, the study shows that AAV2/9-mediated gene expression is influenced by animal gender but not mouse genotype and is insensitive to the presence of lung inflammation. Lower expression levels were observed in male compared with female mice, and transient immunosuppression with dexamethasone significantly reduced the development of NAB in both genders of mice. The study thus advances this serotype for further development and use as a therapeutic vector

Tendon healing induced by chemically modified mRNAs

Tendon disorders are frequent both in human and veterinary medicine with high re-injury rates and unsatisfactory therapeutic treatments. Application of naked chemically modified mRNA (cmRNA) encoding for a therapeutic protein, presents itself as an innovative approach addressing tendon healing. In the current study, we demonstrate that injection of naked cmRNA in glucose-containing solution into tendons results in high protein expression in healthy and experimentally injured tendons. Injection of BMP-7 encoding cmRNA resulted in increased BMP-7 protein expression, less fulminant degradation of collagen type I, decreased collagen type III formation as well as trends towards higher collagen I/III ratio and chemotactic cell attraction in surgically dissected tendons compared to vehicle treatment. Moreover reporter protein encoding cmRNA was injected into acute tendon injuries in a highly translational sheep model, revealing wide spread and profound tissue transfection in pathologically affected tissue. Summarizing, these results demonstrate the potential of cmRNAs encoding for therapeutic proteins as a new class of drugs for the treatment of tendon disorders

Translation of angiotensin-converting enzyme 2 upon liver- and lung-targeted delivery of optimized chemically modified mRNA

Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2) protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA) leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT) is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models