Programmable self-assembly of three-dimensional nanostructures from 10,000 unique components

International audienceNucleic acids (DNA and RNA) are widely used to construct nanometre-scale structures with ever increasing complexity, with possible application in fields such as structural biology, biophysics, synthetic biology and photonics. The nanostructures are formed through one-pot self-assembly, with early kilodalton-scale examples containing typically tens of unique DNA strands. The introduction of DNA origami, which uses many staple strands to fold one long scaffold strand into a desired structure, has provided access to megadalton-scale nanostructures that contain hundreds of unique DNA strands. Even larger DNA origami structures are possible, but manufacturing and manipulating an increasingly long scaffold strand remains a challenge. An alternative and more readily scalable approach involves the assembly of DNA bricks, which each consist of four short binding domains arranged so that the bricks can interlock. This approach does not require a scaffold; instead, the short DNA brick strands self-assemble according to specific inter-brick interactions. First-generation bricks used to create three-dimensional structures are 32 nucleotides long, consisting of four eight-nucleotide binding domains. Protocols have been designed to direct the assembly of hundreds of distinct bricks into well formed structures, but attempts to create larger structures have encountered practical challenges and had limited success. Here we show that DNA bricks with longer, 13-nucleotide binding domains make it possible to self-assemble 0.1-1-gigadalton, three-dimensional nanostructures from tens of thousands of unique components, including a 0.5-gigadalton cuboid containing about 30,000 unique bricks and a 1-gigadalton rotationally symmetric tetramer. We also assembled a cuboid that contains around 10,000 bricks and about 20,000 uniquely addressable, 13-base-pair 'voxels' that serves as a molecular canvas for three-dimensional sculpting. Complex, user-prescribed, three-dimensional cavities can be produced within this molecular canvas, enabling the creation of shapes such as letters, a helicoid and a teddy bear. We anticipate that with further optimization of structure design, strand synthesis and assembly procedure even larger structures could be accessible, which could be useful for applications such as positioning functional components

Infection rates associated with epidural indwelling catheters for seven days or longer: systematic review and meta-analysis

Abstract Background To determine infection rate with use of epidural catheters in place for seven days or more. Methods Systematic review and pooled analysis of observational studies. Results Twelve studies with 4,628 patients (median 197 patients) provided information, of which nine (4,334 patients) were published after 1990. Eight studies (3,893 patients) were retrospective, and four studies (735 patients) prospective. Electronic searches identified three studies and searching reference lists nine. There were 257 catheter-related infections in total, of which 211 were superficial and 57 deep, giving rates of 6.1%, 4.6% and 1.2% respectively. Ten of the 12 studies had deep infection rates of 2% or less. The incidence of deep infection was 1 per 2391 days of treatment, or 0.4 per 1000 catheter treatment days. In nine studies (1503 patients), predominantly in cancer, and with average catheter duration of 74 days, the deep infection rate was 2.8%. The proportion of patients with infection of any type was higher in cancer patients with longer catheter duration. Limited numbers of events meant that no reliable estimate of the impact of prospective and retrospective design could be made. There appeared to be a relationship between catheter duration and infection rate from this and other recent estimates. Four of 57 (7%) patients with deep infection died. Conclusion The best estimate is that one person in 35 with an epidural catheter in place for 74 days for relief of cancer pain can be expected to have a deep epidural infection, and that about 1 in 500 may die of infection-related causes. This is a most uncertain estimate given the limited nature of the evidence.</p