Axial - MIT #1
Analysis of exciting MIT life sciences inventors and their inventions
Centered around engineering, MIT takes a unique approach to solving important problems in life sciences. Together with Harvard, the two universities support the rich life sciences ecosystem in Boston.
Studying how complex molecular circuits function and evolve.
The Regev lab is a pioneer in the use of single-cell tools to understand disease - https://www.cell.com/cell/fulltext/S0092-8674(18)31178-4- did single-cell RNA sequencing on melanoma cells to predictive signatures of resistance; discovering CDK4/6 inhibition subverts an important resistance mechanism.
Using ATAC-seq and Hi-C to characterized chromatin accessibility in CD4+ T-cells - https://www.nature.com/articles/s41588-018-0156-2
Overview of the power of single-cell genomics -https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438464/
The invention of a powerful tool Peturb-Seq for single-cell pooled genetic screens - https://www.cell.com/cell/fulltext/S0092-8674(16)31610-5- forming the basis of Coral Genomics:
Inventing expansion microscopy (ExM) forming the basis of Expansion Technologies - http://syntheticneurobiology.org/PDFs/18.12.wassie.FULL.pdf - enabling high resolution imaging of proteins and RNAs within a cell. Exm relies on two previous inventions: swellable polyelectrolyte hydrogels and polymer hydrogels for biological embedding:
Using ExM with lattice light-sheet microscopy to image an entire fly-brain at a nm resolution - http://syntheticneurobiology.org/PDFs/19.01.gao.FULL.pdf
Inventing a non-invasive method to stimulate deep regions of the brain without affecting overlying regions like the cortex - http://syntheticneurobiology.org/PDFs/17.06.grossman.FULL.pdf - relying on temporal interference between multiple electric fields. Next step is to determine how small the focal volume can be for simulation:
Overview of optogenetics from one of its inventors - http://syntheticneurobiology.org/PDFs/15.09.boyden.pdf
Inventing biomolecular materials.
Using a virus to direct the templating of a Pt–Ni(OH)2 structure - https://www.sciencedirect.com/science/article/pii/S2211285518309960
Developing a bio-templated method to produce LiMnBO3 nanoparticles - https://pubs.rsc.org/en/content/articlelanding/2016/gc/c6gc00273k#!divAbstract - providing a pathway to sustainably produce materials for electrodes.
Relying on a virus-template method to generate a chromophore network - https://www.nature.com/articles/nmat4448 - in order to gain precise control of solar energy conversion.
Studying non-coding RNA.
Discovering and characterizing a 4 component non-coding RNA regulatory network - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559361/
In zebrafish, mapping out long intervening noncoding RNAs (lincRNAs) - http://bartellab.wi.mit.edu/publication_reprints/Ulitsky_Cell_2013_Supp.pdf
Analyzing primary microRNAs (pri-miRNAs) to discover features that promote processing into functional miRNAs - http://bartellab.wi.mit.edu/publication_reprints/Fang2015MolCell.pdf
Developing a method to identify circular RNAs (circRNAs) - http://bartellab.wi.mit.edu/publication_reprints/Guo_GenomeBiology14 - suggesting functions beyond being an miRNA sponge.
Leading the way at the interface of biological and materials engineering.
One of the world’s greatest engineers having driven the formation of many new companies and carrying the weight for about half of Polaris’ portfolio -https://www.nature.com/articles/s41573-018-0006-z - with Carl June and others, doing a great review on the power of drug delivery systems to improve response rates to immunotherapies:
Inventing a culture system relying on engineering the ECM to support the growth of intenstinal stem cells - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735007/ - with applications for cell therapy production and organoid design.
Developing a method to delivery drugs into deep parts of the brain called MiNDS - http://stm.sciencemag.org/cgi/pmidlookup?view=short&pmid=29367347 - relying on EEG to monitor delivery/activity and an implantable system to deliver the molecules:
Overview of the importance to deliver drugs through the GI tract and the power of biomaterials to accomplish this goal - https://www.nature.com/articles/519S19a
Squeezing a cell with a microfluidic system to support intracellular delivery into cells - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568376 - driving the founding of SQZ:
Inventing regenerative tools.
One of the most exciting bioengineers in the world, using human liver models to design nucleic-acid therapies with reduced toxicity - https://lmrt.mit.edu/sites/default/files/1-s2.0-S1550413119300671-main.pdf
Inventing nanosensors to measure protease activity; showing the ability to diagnose/classify prostate cancers by types, retrospectively outperforming the PSA biomarker - https://lmrt.mit.edu/sites/default/files/1805337115.full__1.pdf - with this method forming the basis of Glympse Bio:
Overview of liver models to study liver-specific pathogens and infectious diseases - https://lmrt.mit.edu/sites/default/files/Manuscript_3.pdf
Using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models to profile miRNAs to pre-select patients to test an RNA targeting an miRNA - https://lmrt.mit.edu/sites/default/files/1734.full_.pdf
Overview of the power of nanotechnology to improve biology and medicine - https://lmrt.mit.edu/sites/default/files/Wong_GenesDev_2013.pdf
Inventing a DNA-templated method to produce microtissues - https://lmrt.mit.edu/sites/default/files/Li_DOI_2011_0.pdf
New materials for medicine.
Overview of improvements in mRNA manufacturing and delivery for therapeutic applications - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453548/
Developing an mRNA encoding a humanized anti-HER2 antibody - https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(19)30226-6 - showing improved expressivity and PK/PD profiles in the liver with outstanding work in other tissues:
Overview of small-interfering RNA (siRNA) and the key drivers for therapeutic success especially in the context of Alnylam’s pioneering work to get the first siRNA therapy approved - https://www.sciencedirect.com/science/article/abs/pii/S0169409X19300547?via%3Dihub
Overview of cell therapy manufacturing methods - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594100/
Inventing a polymer for a closed-loop insulin delivery system - https://pubs.acs.org/doi/10.1021/nn400630x - working for around 10 days continuously in mice.
Measuring biology and manufacturing at scale.
Creating a single-cell sequencing method, Seq-Well S^3 (Second-Strand Synthesis), to identify new molecular features for human skin inflammation - https://www.biorxiv.org/content/10.1101/689273v1
Inventing an automated, bench-top biomanufacturing system for biologics called Integrated Scalable Cyto-Technology (InSCyT) - https://www.nature.com/articles/nbt.4262 - with the next steps adding an enzymatic module for insulin production:
Overview of developing new bio-production strains - https://www.sciencedirect.com/science/article/abs/pii/S095816691730191X?via%3Dihub
Using nanowells to implement functional cell screens - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26121321/ - generating unique cell patterns to measure features such as migration and proliferation.
Revealing the design principles of biology.
From one of synthetic biology’s pioneers, an overview of using genetic circuits to improve immunotherapies and cell therapies - https://science.sciencemag.org/content/359/6376/eaad1067
Integrating a genetic circuits in Chinese hamster ovary (CHO) cells - https://www.nature.com/articles/s41589-019-0288-4 - to control N-glycosylation of IgG antibodies:
Forming the basis of Strand Therapeutics, developing self-replicating RNAs - https://www.nature.com/articles/s41598-019-43422-0 - to improve immunotherapies and cancer vaccines.
With Frances Arnold and Yohei Yokobayashi, doing pioneering work to use directed evolution to design genetic circuits - https://www.pnas.org/content/99/26/16587.full
Engineering immunity to treat and prevent human disease.
Designing a molecule, amph-ligand, almost acting as an adjuvant within lymph nodes to boost CAR-T activity - https://science.sciencemag.org/content/365/6449/162 - forming the basis of Elicio Therapeutics:
Designing nanoparticles to specifically deliver small molecules to lymphocytes - https://pubs.rsc.org/en/content/articlelanding/2019/bm/c8bm01208c#!divAbstract
Designing immunogenic peptides to directly activate T-cells in lymph nodes - http://cancerimmunolres.aacrjournals.org/content/early/2018/06/16/2326-6066.CIR-17-0607
Overview of the role of the innate immune system in combination therapies especially with checkpoint inhibitors - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647817/
Inventing new tools to read and write biology.
Inventing an RNA editor for C-to-U conversions (RESCUE) - https://science.sciencemag.org/content/365/6451/382
Developing DNA microscopy - https://www.cell.com/cell/fulltext/S0092-8674(19)30547-1 - for chemically encoded imaging of cells:
One of the most important papers this decade - https://science.sciencemag.org/content/339/6121/819 - showing the power of CRISPR gene editing in human cells: