Robust nucleation control via crisscross polymerization of highly coordinated DNA slats

Minev, Dionis; Wintersinger, Christopher M.; Ershova, Anastasia; Shih, William M.

doi:10.1038/s41467-021-21755-7

“…North et al demonstrated that viral DNA and RNA levels in RT-SHIV-infected, ART-treated macaques were highest in lymphoid tissues including the spleen, lymph nodes, and gastrointestinal (GI) tract [ 21 ]. These results have been confirmed in later studies with more potent ART regimens and longer periods of treatment [ 22 , 23 ]. The central nervous system has also been implicated as a site of viral persistence in NHP models potentially due to poor ART penetrance [ 24 ].…”

Section: Nonhuman Primates For Hiv-1 Cure Researchsupporting

confidence: 55%

New Latency Reversing Agents for HIV-1 Cure: Insights from Nonhuman Primate Models

Bricker

¹

,

Chahroudi

²

,

Mavigner

³

2021

Viruses

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Antiretroviral therapy (ART) controls human immunodeficiency virus 1 (HIV-1) replication and prevents disease progression but does not eradicate HIV-1. The persistence of a reservoir of latently infected cells represents the main barrier to a cure. “Shock and kill” is a promising strategy involving latency reversing agents (LRAs) to reactivate HIV-1 from latently infected cells, thus exposing the infected cells to killing by the immune system or clearance agents. Here, we review advances to the “shock and kill” strategy made through the nonhuman primate (NHP) model, highlighting recently identified latency reversing agents and approaches such as mimetics of the second mitochondrial activator of caspase (SMACm), experimental CD8+ T cell depletion, immune checkpoint blockade (ICI), and toll-like receptor (TLR) agonists. We also discuss the advantages and limits of the NHP model for HIV cure research and methods developed to evaluate the efficacy of in vivo treatment with LRAs in NHPs.

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“…In the TW core, each helper strand weaves in the transverse direction over and under every other scaffold strand four times, forming the densest HJs in 2D DNA lattices with a density of 2HJ per turn. 45 Compared with LW cores having totally 5 HJs and bLW cores totally 4 HJs, the TW core possesses totally 12 HJs.…”

Section: D Arrays Of Transversely Woven (Tw) Tilesmentioning

confidence: 99%

Regulation of 2D DNA Nanostructures by the Coupling of Tile Curvatures and Arm Twists

Jiang¹,

Lu²,

Zhang³

et al. 2021

Preprint

0

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DNA overwinding and underwinding between adjacent Holliday junctions have been applied in DNA origami constructs to design both left-handed and right-handed nanostructures. For a variety of DNA tubes assembled from small tiles, only an abstract concept of the intrinsic tile curvature was previously used to explain their formation. Details regarding the quantitative and structural descriptions of the intrinsic tile curvature and its evolution in DNA tubes by coupling with arm twists have been lacking. In this work, we designed three types of tile cores from a circular 128 nucleotide scaffold by longitudinal weaving (LW), bridging longitudinal weaving (bLW), and transverse weaving (TW) and assembled their 2D planar or tubular nanostructures via inter-tile arms with a distance of an odd or even number of DNA half-turns. The biotin/streptavidin (SA) labeling technique was applied to define the tube configuration with addressable inside and outside surfaces and thus their component tile conformation with addressable concave and convex curvatures. Both chiral tubes possessing left-handed and right-handed curvatures could be generated by finely tuning p and q in bLW-Ep/q designs (bLW tile cores joined together by inter-tile arms of even number of half-turns with the arm length of p base pairs (bp) and the sticky end length of q nucleotides (nt)). We were able to assign the chiral indices (n,m) to each specific tube from the high-resolution AFM images, and thus estimated the tile curvature angle with a regular polygon model that approximates each tube’s transverse section. We attribute the curvature evolution of bLW-Ep/q tubes composed of the same tile core to the coupling of the intrinsic tile curvature and different arm twists. A better understanding of integrated actions of different types of twisting forces on DNA tubes will be much more helpful in engineering DNA nanostructures in the future.

show abstract

“…In the TW core, each helper strand weaves in the transverse direction over and under every other scaffold strand four times, forming the densest HJs in 2D DNA lattices with a density of 2HJ/turn. 45 Compared with LW and bLW cores having 5 and 4 HJs, respectively, the TW core possesses 12 HJs.…”

Section: D Arrays Of Transverse Weaving (Tw) Tilesmentioning

confidence: 99%

Regulation of 2D DNA Nanostructures by the Coupling of Tile Cur-Vatures and Arm Twists

Jiang¹,

Lu²,

Zhang³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

DNA overwinding and underwinding between adjacent Holliday junctions have been applied in DNA origami constructs to design both left-handed and right-handed nanostructures. For a variety of DNA tubes assembled from small tiles, only an abstract concept of the intrinsic tile curvature was previously used to explain their formation. Details regarding the quantitative and structural descriptions of the intrinsic tile curvature and its evolution in DNA tubes by coupling with arm twists have been lacking. In this work, we designed three types of tile cores from a circular 128 nucleotide scaffold by longitudinal weaving (LW), bridging longitudinal weaving (bLW), and transverse weaving (TW) and assembled their 2D planar or tubular nanostructures via inter-tile arms with a distance of an odd or even number of DNA half-turns. The biotin/streptavidin (SA) labeling technique was applied to define the tube configuration with addressable inside and outside surfaces and thus their component tile conformation with addressable concave and convex curvatures. Both chiral tubes possessing left-handed and right-handed curvatures could be generated by finely tuning p and q in bLW-Ep/q designs (bLW tile cores joined together by inter-tile arms of even number of half-turns with the arm length of p base pairs (bp) and the sticky end length of q nucleotides (nt)). We were able to assign the chiral indices (n,m) to each specific tube from the high-resolution AFM images, and thus estimated the tile curvature angle with a regular polygon model that approximates each tube’s transverse section. We attribute the curvature evolution of bLW-Ep/q tubes composed of the same tile core to the coupling of the intrinsic tile curvature and different arm twists. A better understanding of integrated actions of different types of twisting forces on DNA tubes will be much more helpful in engineering DNA nanostructures in the future.

show abstract

Robust nucleation control via crisscross polymerization of highly coordinated DNA slats

Cited by 38 publications

References 46 publications

New Latency Reversing Agents for HIV-1 Cure: Insights from Nonhuman Primate Models

New Latency Reversing Agents for HIV-1 Cure: Insights from Nonhuman Primate Models

Regulation of 2D DNA Nanostructures by the Coupling of Tile Curvatures and Arm Twists

Regulation of 2D DNA Nanostructures by the Coupling of Tile Cur-Vatures and Arm Twists

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