Size does matter: overcoming the adeno-associated virus packaging limit

Recombinant adeno-associated virus (rAAV) vectors mediate long-term gene transfer without any known toxicity. The primary limitation of rAAV has been the small size of the virion (20 nm), which only permits the packaging of 4.7 kilobases (kb) of exogenous DNA, including the promoter, the polyadenylation signal and any other enhancer elements that might be desired. Two recent reports (D Duan et al: Nat Med 2000, 6:595-598; Z Yan et al: Proc Natl Acad Sci USA 2000, 97:6716-6721) have exploited a unique feature of rAAV genomes, their ability to link together in doublets or strings, to bypass this size limitation. This technology could improve the chances for successful gene therapy of diseases like cystic fibrosis or Duchenne muscular dystrophy that lead to significant pulmonary morbidity

Recent Findings Concerning PAMAM Dendrimer Conjugates with Cyclodextrins as Carriers of DNA and RNA

We have evaluated the potential use of various polyamidoamine (PAMAM) dendrimer [dendrimer, generation (G) 2-4] conjugates with cyclodextrins (CyDs) as novel DNA and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer (G3) conjugate with α-CyD having an average degree of substitution (DS) of 2.4 [α-CDE (G3, DS2)] displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of α-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended α-CDEs. Of the various sugar-appended α-CDEs prepared, galactose- or mannose-appended α-CDEs provided superior gene transfer activity to α-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended α-CDE [Lac-α-CDE (G2)] was found to possess asialoglycoprotein receptor (AgpR)-mediated hepatocyte-selective gene transfer activity, both in vitro and in vivo. Most recently, we prepared folate-poly(ethylene glycol)-appended α-CDE [Fol-PαC (G3)] and revealed that Fol-PαC (G3) imparted folate receptor (FR)-mediated cancer cell-selective gene transfer activity. Consequently, α-CDEs bearing integrated, multifunctional molecules may possess the potential to be novel carriers for DNA, shRNA and siRNA

Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)

In recent years, the development of powerful viral gene transfer techniques has greatly facilitated the study of gene function. This review summarises some of the viral delivery systems routinely used to mediate gene transfer into cell lines, primary cell cultures and in whole animal models. The systems described were originally discussed at a 1-day European Tissue Culture Society (ETCS-UK) workshop that was held at University College London on 1st April 2009. Recombinant-deficient viral vectors (viruses that are no longer able to replicate) are used to transduce dividing and post-mitotic cells, and they have been optimised to mediate regulatable, powerful, long-term and cell-specific expression. Hence, viral systems have become very widely used, especially in the field of neurobiology. This review introduces the main categories of viral vectors, focusing on their initial development and highlighting modifications and improvements made since their introduction. In particular, the use of specific promoters to restrict expression, translational enhancers and regulatory elements to boost expression from a single virion and the development of regulatable systems is described

TINJAUAN TEORI PERUNDANG-UNDANGAN TERHADAP UNDANG-UNDANG NOMOR 11 TAHUN 2012 TENTANG SISTEM PERADILAN PIDANA ANAK

Teori Perundang-Undangan berorientasi pada mencari kejelasan, kejernihan makna atau pengertian dan bersifat kognitif. Artinya, Teori PerundangUndangan menekankan bukan pada proses pembentukan peraturan perundangUndangan, namun menekankan pada bagaimana membentuk materi Peraturan Perundang-Undangan. Dalam membentuk materi pada Undang-Undang Nomor 11 Tahun 2012 tentang Sistem Peradilan Pidana Anak harus berpedoman pada dasardasar dalam penyusunan Peraturan perundang-undangan dan memperhatikan tujuan dari Undang-Undang Sistem Peradilan Pidana Anak itu sendiri. Tujuan dibentuknya Undang-Undang Sistem Peradilan Pidana Anak adalah untuk dapat mewujudkan peradilan yang benar-benar menjamin perlindungan terbaik terhadap anak yang berhadapan dengan hukum. Kata Kunci : Teori Perundang-Undangan, Sistem Peradilan Pidana Ana