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This 2020 study added a SORT component to lipid nanoparticles to alter tissue targeting and deliver mRNA or CRISPR cargoes. It provides preclinical evidence for extrahepatic delivery, rather than proof of human tissue targeting or clinical benefit.
Combining cryogenic specimen preparation with three-dimensional electron diffraction, researchers followed glycine crystallization from water. Different samples captured the sequential appearance of its three ambient-pressure polymorphs, including a short-lived beta form before alpha became dominant. Structures could be obtained from very small crystallites, demonstrating how diffraction can reveal phases missed by slower bulk measurements.
This outlook places three-dimensional electron diffraction within the wider development of nanocrystallography. It discusses acquisition and analysis approaches, the treatment of diffraction from very small crystals, and applications spanning organic, inorganic, and biological materials. Pharmaceutical examples help connect the methodological landscape with molecular crystal analysis, while the article remains a synthesis rather than a new API validation study.
Researchers solved the previously unknown crystal structure of orthocetamol, a pharmaceutical compound that had not yielded single crystals suitable for X-ray diffraction. The approach combined low-dose three-dimensional electron-diffraction acquisition with a single-electron detector. The case illustrates structure determination from challenging small crystals rather than requiring successful growth of larger specimens first.
A complete structure analysis of a sofosbuvir–L-proline pharmaceutical cocrystal used electron diffraction from a highly beam-sensitive nanocrystal. Collecting data at multiple positions and using improved intensity extraction enabled structure solution. Dynamical diffraction effects then distinguished the absolute structure despite the sample containing light atoms, establishing an important route to stereochemical assignment.
This review explains MicroED and compares its role with other structure-determination methods. It surveys example structures and practical considerations for prospective users, including the progression from specimen preparation to diffraction acquisition and analysis. Its value for pharmaceutical readers is methodological orientation across sample classes, rather than evidence that a specific API screening workflow has been validated.
Researchers demonstrated atomic-resolution structure determination of small organic molecules from nanocrystals present in ordinary powders, using minimal specimen preparation. The study included pharmaceutical and natural-product examples and showed that individual compounds could be analyzed from a mixed specimen. It established a practical route around the need to grow crystals large enough for conventional single-crystal X-ray diffraction.
A prototype electron diffractometer combined a transmission electron microscope with a hybrid pixel detector. Researchers determined a methylene blue derivative and identified the crystal structure of paracetamol within a commercial medicine containing crystalline and noncrystalline components. The work demonstrated chemical crystallography from crystals too small for standard X-ray workflows, while emphasizing the need for appropriate structural validation.
Researchers determined crystal structures of ramelteon and tolvaptan using three-dimensional precession electron diffraction tomography on approximately 500-nanometer crystals. Structures from subsequently grown, much larger crystals were measured by single-crystal X-ray diffraction for comparison. Agreement in molecular conformation, packing, and unit-cell parameters supported the electron-diffraction workflow for these two pharmaceutical materials.
Historical methods study (2017): 213 sites from 11 academic trials were randomised; audits covered 156 sites and 1,618 patients. Risk-adapted monitoring met the specified non-inferiority criterion for major audit findings while using fewer resources. High-risk trials were excluded. The findings inform monitoring design, not the performance of any Chinese CRO.
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