Pig-to-Human Kidney Transplants: Codon Index #50
Plus: Larger E. coli divide faster (yes, really).
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In the final months of 2021, though — before David Bennett Sr. received his genetically-modified pig heart — another experiment was underway within the intensive care unit at New York University Langone Hospital. Two pig kidneys were transplanted into brain-dead people and monitored over a 54-hour period. Both kidneys immediately produced urine and biopsies did not reveal any signs of organ rejection.
Since the two people who received the organs were “recently deceased,” the Food and Drug Administration did not require that the researchers first submit an Investigational New Drug application, according to the paper. Thus, the transplants were overseen by a little-known NYU committee.
At any given time, there are about 100,000 people in the United States waiting on an organ transplant list. Pigs have emerged as “the most acceptable donor species for xenotransplantation into humans,” according to the new study, but they express an enzyme called alpha-1,3-galactosyltransferase that, when detected by a human host, can trigger an immune response.
For the new study, researchers first deleted the gene encoding alpha-1,3-galactosyltransferase. During the 54-hour period, each corpse was injected with 1 gram of methylpredniose (daily) and 1 gram of mycophenolate mofetil (twice daily) to suppress the immune system. Both kidneys remained “pink” and healthy throughout the study and there was “no clinical evidence of dysregulated coagulation, complement, systemic inflammation, or recipient instability.”
The recent heart transplants likely failed because the organ was infected with a pig virus, according to MIT Technology Review. But the authors of this latest study detected no such viruses in the two kidneys, which may soon make their way into the living.
Read more at The New England Journal of Medicine.
(↑ = recommended article, * = open access, † = review article )
↑↑*Featured: The energy cost and time requires to build a bacterial cell does not scale with size; in other words, larger cells actually divide faster than smaller cells, according to evidence from a 60,000-generation E. coli experiment. Long-term experimental evolution decouples size and production costs in Escherichia coli. Marshall DJ…McDonald MJ. PNAS. Link
↑*Enzymatically-active bacterial microcompartments follow substrate gradients and are protected from aggregation in a cell-free system. Steinkühler J…Kamat NP. bioRxiv (preprint). Link
↑Distinct gene clusters drive formation of ferrosome organelles in bacteria. Grant CR…Komeili A. Nature. Link
Compatibility rules of human enhancer and promoter sequences. Bergman DT…Engreitz JM. Nature. Link
Fast and efficient DNA replication with purified human proteins. Baris Y…Yeeles JTP. Nature. Link
↑Birth of mice from meiotically arrested spermatocytes following biparental meiosis in halved oocytes. Ogonuki N…Ogura A. EMBO Reports. Link
Efficient Synthesis of Phycocyanobilin by Combinatorial Metabolic Engineering in Escherichia coli. Zhao X…Zhou J. ACS Synthetic Biology. Link
†Extracellular Optogenetics at the Interface of Synthetic Biology & Materials Science. Månsson LK, Pitenis AA & Wilson MZ. Frontiers in Bioengineering and Biotechnology. Link
Engineering of a TrpR-Based Biosensor for Altered Dynamic Range and Ligand Preference. Gong X…Yan Y. ACS Synthetic Biology. Link
Computational Tools & Models
↑*Signal Peptide Efficiency: from High-throughput Data to Prediction and Explanation. Grasso S…van Rij T. bioRxiv (preprint). Link
*IBS 2.0: an upgraded illustrator for the visualization of biological sequences. Xie Y…Ren J. Nucleic Acids Research. Link
*Codon-specific Ramachandran plots show amino acid backbone conformation depends on identity of the translated codon. Rosenberg AA, Marx A & Bronstein AM. Nature Communications. Link
CRISPR & Genetic Control
*Engineered Cas12i2 is a versatile high-efficiency platform for therapeutic genome editing. McGaw C…Chong S. Nature Communications. Link
*Multiplex base- and prime-editing with drive-and-process CRISPR arrays. Yuan Q & Gao X. Nature Communications. Link
†CRISPR-Cas-mediated diagnostics. Li L…Lin P. Trends in Biotechnology. Link
*Efficient Single-Nucleotide Microbial Genome Editing Achieved Using CRISPR/Cpf1 with Maximally 3′-End-Truncated crRNAs. Lee HJ…Lee SJ. ACS Synthetic Biology. Link
Medicine & Diagnostics
*Hierarchical self-uncloaking CRISPR-Cas13a–customized RNA nanococoons for spatial-controlled genome editing and precise cancer therapy. Fan N…Cheng W. Science Advances. Link
Efficient CRISPR/Cas9 nickase-mediated genome editing in an in vitro model of mucopolysaccharidosis IVA. Leal AF & Alméciga-Díaz CJ. Gene Therapy. Link
*Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro. Zeng L…Qi LS. Nature Communications. Link
*Ultrapotent and Broad Neutralization of SARS-CoV-2 Variants by Modular, Tetravalent, Bi-paratopic Antibodies. Miersch S…Sidhu SS. Cell Reports. Link
*Adaptation-proof SARS-CoV-2 vaccine design. Vishweshwaraiah YL…Dokholyan NV. bioRxiv (preprint). Link
*Polymer-coated carbon nanotube hybrids with functional peptides for gene delivery into plant mitochondria. Law SSY…Numata K. Nature Communications. Link
Protein & Molecular Engineering
↑*†In vivo hypermutation and continuous evolution. Molina RS…Liu CC. Nature Reviews Methods Primers. Link
Ex silico engineering of cystine-dense peptides yielding a potent bispecific T cell engager. Crook ZR…Olson JM. Science Translational Medicine. Link
Tools & Technology
↑*PlasmidMaker is a versatile, automated, and high throughput end-to-end platform for plasmid construction. Enghiad B…Zhao H. Nature Communications. Link
*Exogenous loading of extracellular vesicles, virus-like particles, and lentiviral vectors with supercharged proteins. Breyne K…Breakefield XO. Communications Biology. Link
*Identification of adeno-associated virus variants for gene transfer into human neural cell types by parallel capsid screening. Flitsch LJ…Brüstle O. Scientific Reports. Link
*Vulnerability and the Ethics of Human Germline Genome Editing. Labude MK…Mills C. The CRISPR Journal. Link