From conception to COVID‐19: an arduous journey of tribulations of racism and triumphs

Abstract

The densely wooded 800‐acre Madras Christian College (MCC) campus, India where I lived most of my early years, sparked my curiosity in plants. Observing the pitcher plant that captured insects, trees that produced fruits in the shape of a human skull, wild orchids, bright wildflowers, and dense vegetation amidst monsoon rains was exciting but also scary due to the wildlife, especially foxes and snakes. I was born in Salem, India, located at the foothills of mountains, tenth in a family of twelve, where my father was a high court judge.

Green giant—a tiny chloroplast genome with mighty power to produce high‐value proteins: history and phylogeny

“…When the largest human blood protein (FVIII, 185 kDa monomer, with pentamer assembly) was expressed in the chloroplast, the level reached industry expectations for commercial scale production and clinical evaluation (Kwon et al ., 2018). Codon optimised expression of angiotensin‐converting enzyme 2 not only helped to treat pulmonary hypertension, but has also now been tested in the clinic to treat COVID‐19 patients (Daniell, 2020), as discussed in depth below. Codon‐optimized expression of a novel human insulin‐like growth factor in lettuce chloroplasts promoted musculoskeletal cell proliferation, differentiation and diabetic bone fracture healing (Park et al ., 2020).…”

“…Most importantly, a selectable antibiotic resistance gene has been removed from transplastomic chloroplast genomes in edible crops (Daniell et al ., 2019b; Kumari et al ., 2019; Park et al ., 2020). Production of protein drugs in cGMP facilities, long‐term stability of drugs in freeze‐dried plant cells (Daniell, 2020; Daniell et al ., 2019b; Daniell et al ., 2019c; Park et al ., 2020; Su et al ., 2015), evaluation of drug substance by toxicology and pharmacokinetic studies (Daniell et al ., 2019c) and recent FDA approval of PDs orally delivered peanut cells to treat allergy (Tilles and Petroni, 2018; Vickery et al ., 2018) all represent major recent advances in this field. Based on these recent advances, the next decade should be particularly promising for the common use of proteins made in chloroplasts to enhance human health and well‐being.…”

“…Similar codon optimization of the CTB‐FVIII‐LC gene resulted in successful expression of the largest human blood protein (FVIII, 185 kDa monomer, with pentamer assembly) in chloroplasts (Kwon et al ., 2018), and this has now advanced to commercial production and clinical trials. Codon‐optimized Ace2 is now tested in the clinic to treat COVID‐19 patients (Daniell, 2020).…”

“…Fibrosis and pulmonary vessel wall thickness, which are the symptoms observed in COVID‐19 patients. For further details, see Daniell (2020).…”

“…Most importantly, ACE2 produces anti‐inflammatory, cytoprotective angiotensin 1‐7 (Ang 1‐7) peptide via cleavage of the vasoconstrictor angiotensin II (AngII). Of potential therapeutic relevance, oral delivery of both ACE2 and Ang1‐7 bioencapsulated in plant cells significantly decreased right ventricular systolic pressure and improved pulmonary blood flow and right ventricle function in diseased hypertensive animals (Daniell, 2020; Shenoy et al ., 2014; Figure 2). Conceivably, therapeutic delivery of ACE2/Ang1‐7 could also be employed to restore a more favourable balance of Ang II and Ang 1‐7 in patients with COVID‐19 disease.…”