Immune engineering: From systems immunology to engineering immunity

Abstract

The smallpox vaccine represents the earliest attempt in engineering immunity. The recent success of chimeric antigen receptor T cells (CAR-T cells) in cancer once again demonstrates the clinical potential of immune engineering. Inspired by this success, diverse approaches have been used to boost various aspects of immunity: engineering dendritic cells (DCs), natural killer (NK) cells, T cells, antibodies, cytokines, small peptides, and others. With recent development of various high-throughput technologies (of which engineers, especially biomedical engineers/bioengineers contributed significantly), such as immune repertoire sequencing, and analytical methods, a systems level of understanding immunity (or the lack of it) beyond model animals has provided critical insights into the human immune system. This review focuses on recent progressed made in systems biology and the engineering of adaptive immunity.

Simultaneous multiplexed amplicon sequencing and transcriptome profiling in single cells

“…Antibodies are comprised of heavy 25 (μ, α, γ, δ, ε) and light chains (κ, λ), linked by disulfide bonds (Fig 3b). Each chain contains 26 variable and constant domains. The variable region of the heavy chain is comprised of 27 variable (V), diversity (D) and joining (J) segments, whereas the variable region of the 28 light chain consists of a V and J segment (Fig 3b).…”

“…Here, we 24 present example designs with 7-10 amplicons. The design and ratio of probes can be 25 tailored to individual applications allowing researchers the flexibility to use their existing 26 scRNA-seq set-up for a wide variety of biological measurements. 27 28 10 We have highlighted two potential applications of DART-seq technology.…”

“…6 7 We further applied DART-seq to measure endogenously paired, heavy and light chain 8 amplicons within the transcriptome of human B lymphocyte cells in a mixed human PBMC 9 population, while having access to full transcriptome data of all other cell types (Fig 3). 10 Determination of the paired antibody repertoire at depth can provide insights into several 11 medically and immunologically relevant issues, including vaccine design and 12 deployment [24][25][26] . 1 2 Primer bead synthesis.…”

“…24 25 DART-seq is easy to implement and enables a range of new biological measurements. 26 Here, we explored two applications. We first applied DART-seq to profile viral-host 27 interactions and viral genome dynamics in single cells.…”

“…Briefly, cells and barcoded primer beads are co- 25 encapsulated in droplets using a microfluidic device. Cellular RNA is captured by the 26 primer beads, and is reverse transcribed after breaking the droplets. The DART-seq 27 beads prime reverse transcription of both A-tailed mRNA transcripts and RNA segments 28 complementary to the custom primers ligated to the beads (Fig 1c).…”