LASSO for Standardized, High-Throughput RNA Workflows

Team Dynamic Matrices | 10 September 2026

In our post on why RNA workflows fail reproducibility we argued that the largest sources of run-to-run variance are lot-variable biological reagents, operator-dependent timing, and the way both compound at scale. Most of that variance enters not at extraction but at the step right after it: rRNA depletion or target capture. Enzymatic digestion and magnetic-bead binding are exactly the kinds of steps that vary. LASSO was built to take them out of the workflow. This post is what it does, with the numbers, and where it fits.

A defined chemistry instead of a variable one

riboLASSO removes rRNA using a library of sequence-specific DNA catcher strands attached to a soluble polymer. Hybridisation to rRNA crosslinks the polymer network, which condenses into a pellet; the supernatant is your depleted RNA. There is no RNase H step, no DNase step, no streptavidin bead, and no magnetic rack.

Because the chemistry is defined by sequence and by a synthetic polymer made to specification, it behaves the same from one manufactured batch to the next. In our validation on human total RNA we measure over 98 percent rRNA depletion, with about seven times fewer off-target outlier samples than bead-based or enzymatic comparators in the same hands. Residual rRNA is the largest single waste of sequencing budget in most pipelines; our cost post puts numbers on it.

Fewer manual steps, fewer places for variance to enter

Every wash, bead separation and timed digestion is a point where two operators, or one operator on two days, diverge. riboLASSO catcher strands come pre-configured: add total RNA, incubate, spin, take the supernatant. Hands-on time is under 5 minutes per sample and under 15 minutes for a full 24-sample run. There is no step that has to be stopped at the right moment, because the capture goes to completion and stays there.

Built to extend, not just to deplete

rRNA depletion is one application of the LASSO capture platform. LASSOflex applies the same chemistry to custom DNA, RNA or protein targets, so a lab is not locked into one panel. A workflow that has to be re-qualified for every new sample type is not standardised; one that extends by adding catcher strands is.

Current validation status, stated plainly:

• Human total RNA: validated and available (riboLASSO Human)
• Mouse and rat: catcher libraries in validation
• Pan-bacterial rRNA: catcher library designed, validation planned
• Globin depletion for blood: planned
• Custom targets (LASSOflex): available as a design service with per-target validation data

If your organism or target is not on the list, ask; the design pipeline is the same.

Where it sits in your pipeline

riboLASSO works on RNA that has already been extracted. It replaces the depletion step, not the extraction. Upstream, your extraction and QC stay as they are (we suggest the four-checkpoint system). Downstream, the depleted RNA goes into any standard library prep.

Practical details:

• Storage: about one year at 4 °C. No freezer, no cold-chain scheduling.
• Cost: less than half of comparable commercial depletion kits per sample at our current pricing, which matters at volume.
• Equipment: a heat block and a benchtop centrifuge.
• Status: pilot phase. We are working directly with early-access labs to validate it against their own pipelines and sample types, and we publish spread, not only means.

What it does not fix

It does not fix upstream variance in collection, stabilisation, lysis or extraction. Those still need the audit we describe elsewhere. And it does not yet have the decade of literature that bead and enzymatic methods carry; we are building that record with pilot partners now.