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Targeted delivery of nucleic acid therapeutics to the lungs could transform treatment options for pulmonary disease. We have previously developed oligomeric charge-altering releasable transporters (CARTs) for in vivo mRNA transfection and demonstrated their efficacy for use in mRNA-based cancer vaccination and local immunomodulatory therapies against murine tumors. While our previously reported glycine-based CART-mRNA complexes ( G-CARTs/ mRNA) show selective protein expression in the spleen (mouse, >99%), here, we report a new lysine-derived CART-mRNA complex (K-CART/ mRNA ) that, without additives or targeting ligands, shows selective protein expression in the lungs (mouse, >90%) following systemic IV administration. We further show that by delivering siRNA using the K-CART , we can significantly decrease expression of a lung-localized reporter protein. Blood chemistry and organ pathology studies demonstrate that K-CARTs are safe and well-tolerated. We report on the new step economical, organocatalytic synthesis (two steps) of functionalized polyesters and oligo-carbonate-co-α-aminoester K-CARTs from simple amino acid and lipid-based monomers. The ability to direct protein expression selectively in the spleen or lungs by simple, modular changes to the CART structure opens fundamentally new opportunities in research and gene therapy.

RNA technology is transforming life science research and medicine, but many applications are limited by the accessibility, cost, efficacy, and tolerability of delivery systems. Here we report the first members of a new class of dynamic RNA delivery vectors, oligo(serine ester)-based charge-altering releasable transporters (Ser-CARTs). Composed of lipid-containing oligocarbonates and cationic oligo(serine esters), Ser-CARTs are readily prepared (one flask) by a mild ring-opening polymerization using thiourea anions and, upon simple mixing with mRNA, readily form complexes that degrade to neutral serine-based products, efficiently releasing their mRNA cargo. mRNA/Ser-CART transfection efficiencies of >95% are achieved in vitro. Intramuscular or intravenous (iv) injections of mRNA/Ser-CARTs into living mice result in in vivo expression of a luciferase reporter protein, with spleen localization observed after iv injection.

Academics researchers and "citizen scientists" from 22 countries confirmed that yellow mealworms, the larvae of Tenebrio molitor Linnaeus, can survive by eating polystyrene (PS) foam. More detailed assessments of this capability for mealworms were carried out by12 sources: five from the USA, six from China, and one from Northern Ireland. All of these mealworms digested PS foam. PS mass decreased and depolymerization was observed, with appearance of lower molecular weight residuals and functional groups indicative of oxidative transformations in extracts from the frass (insect excrement). An addition of gentamycin (30 mg g -1 ), a bactericidal antibiotic, inhibited depolymerization, implicating the gut microbiome in the biodegradation process. Microbial community analyses demonstrated significant taxonomic shifts for mealworms fed diets of PS plus bran and PS alone. The results indicate that mealworms from diverse locations eat and metabolize PS and support the hypothesis that this capacity is independent of the geographic origin of the mealworms, and is likely ubiquitous to members of this species., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

RNAs are a promising class of therapeutics given their ability to regulate protein concentrations at the cellular level. Developing safe and effective strategies to deliver RNAs remains important for realizing their full clinical potential. Here, we develop lipid nanoparticle formulations that can deliver short interfering RNAs (for gene silencing) or messenger RNAs (for gene upregulation). Specifically, we study how the tail length, tail geometry, and linker spacing in diketopiperazine lipid materials influences LNP potency with siRNAs and mRNAs. Eight lipid materials are synthesized, and 16 total formulations are screened for activity in vitro; the lead material is evaluated with mRNA for in vivo use and demonstrates luciferase protein expression in the spleen. In undertaking this approach, not only do we develop synthetic routes to delivery materials, but we also reveal structural criteria that could be useful for developing next-generation delivery materials for RNA therapeutics., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T-cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non-Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose-dependent and time-controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells. Here, the design, synthesis, and biological evaluation of a lipid nanoparticle (LNP) system that can encapsulate mRNA, navigate to the spleen, transfect B lymphocytes, and induce more than 60 pg of protein expression per million B cells within the spleen is described. Importantly, this LNP induces more than 85% of total protein production in the spleen, despite LNPs being observed transiently in the liver and other organs. These results demonstrate that LNP composition alone can be used to modulate the site of protein induction in vivo, highlighting the critical importance of designing and synthesizing new nanomaterials for nucleic acid delivery., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Thousands of human diseases could be treated by selectively controlling the expression of specific proteins in vivo. A new series of alkenyl amino alcohol (AAA) ionizable lipid nanoparticles (LNPs) capable of delivering human mRNA with unprecedented levels of in vivo efficacy is demonstrated. This study highlights the importance of utilizing synthesis tools in tandem with biological inspiration to understand and improve nucleic acid delivery in vivo., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Granulocytic sarcoma (chloroma) is a rare tumor almost always associated with leukemia. Intraaxial brain lesions are rare, and can mimic infection or primary neoplasm. This intracerebellar chloroma arose after autologous bone marrow transplantation in a 29-year-old woman with leukemia. On T1-weighted MR images, the lesion was isointense with gray matter, and enhanced homogeneously. On T2-weighted and proton density-weighted MR sequences, the center was isointense with gray matter and the periphery was isointense with white matter. The lesion's tendency to remain isointense on sequences with long repetition times is presumably attributable to the presence of myeloperoxidase.

Objective: To define the role of contrast-enhanced magnetic resonance imaging (MRI) as a possible adjunct to funduscopy and ultrasonography in a selected sample of non-neoplastic disorders of the chorioretina., Patients and Methods: The study group consisted of five patients (ranging in age from 3 to 78 years) with one of the following diagnoses: ocular toxocariasis, staphyloma, glaucoma, or ocular involvement of cytomegalovirus (CMV) infection or AIDS. All of the patients underwent MRI, and the findings were correlated with those of funduscopy and ultrasonography when possible., Results: There were two abnormal MRI enhancement patterns, one with and the other without major distortion of the chorioretina. Areas of abnormal enhancement correlated well with the funduscopic findings. For the patient with CMV infection and the one with AIDS, who were not examined with ultrasonography, MRI showed subtle chorioretinal abnormalities. In the other three cases, for which both ultrasonography and MRI were performed, the findings of the two methods correlated well., Conclusions: Ultrasonography remains the imaging modality of choice in the work-up of most ocular abnormalities. Ultrasonography, MRI and computed tomography are recommended when funduscopy is technically not possible. Because contrast-enhanced MRI is often performed to define the remainder of the orbit, as well as extra-orbital structures, and because of its capability to demonstrate abnormalities of the chorioretina, this modality may serve as a useful adjunct to ultrasonography. Further studies are needed to compare the efficacy of contrast-enhanced MRI and ultrasonography in the evaluation of small, nonneoplastic lesions of the chorioretina.

Most documented cases of radiation-induced optic neuropathy are unilateral and occur more than 1 year after radiotherapy to the sellar region. We describe a patient with bilateral radiation optic neuropathy 3 months following the completion of radiotherapy. MRI 13 months after the onset of visual failure showed bilateral optic atrophy with residual gadolinium enhancement.

During a 3-year period, all inpatients in the psychiatry unit underwent routine screening computed tomography (CT) in an effort to detect clinically unsuspected intracranial abnormalities. Of 261 patients examined who had no focal neurologic deficits, 103 had schizophrenia, 71 had depression, 48 had bipolar disorders, and 39 had paranoid delusions. Findings on 230 (88.1%) of the CT scans were within normal limits, and 27 (10.4%) showed only cortical atrophy. The remaining four cases (1.5%) demonstrated basal ganglia calcification (n = 2), old lacunar infarction (n = 1), or osteoma arising from the inner table of the skull (n = 1), all of which were considered to be clinically unrelated to the patients' psychiatric conditions. In the absence of focal neurologic deficits or other findings suggesting an intracranial abnormality (eg, papilledema, seizures, persistent or increasing headaches), there is no justification for routine CT scanning in patients admitted to the hospital for psychiatric disorders.