Choose the biological problem
A specialist defines a relevant cell model, donor context and function that would matter beyond an aging-clock score.
CRISPR / Research program K09
Proposed program · Partner qualificationCausal Cellular Discovery
Find what changes function. Not just what changes a marker.
The program question
Which controlled change in gene activity improves the useful function of surviving cells while preserving their identity?
Use focused CRISPR interference and activation as tools for understanding cellular dysfunction. The program begins with one tissue-relevant question and a functional endpoint; it does not begin with permanent editing of healthy people.
Separate perturbation from interpretation
Evidence records keep activation, repression and deletion distinct. A marker change must be evaluated alongside survival and population composition.
Build the decision asset
The intended first output is a reproducible target dossier and dataset, with uncertainties and an independently reviewable analysis.
What would justify the next step?
Proceed only with a qualified scientific lead, authorized material and data, a laboratory agreement where needed, and an agreed functional and safety framework. No Karam experiment has been established by this brief.
From question to decision
A program names the scientific direction. A project brief defines a proposed bounded work package. A commercial scope specifies what a buyer would receive and what must be qualified before contracting. These are related, but they are not interchangeable.
Research context
External work. Explicit limits.
2026-07-27 · China
Human cell models · Cas9 screenGNPTAB–STING: separate harmful signaling from maintenance
A focused Cas9 screen identified GNPTAB as a regulator of senescence. The assessment describes a noncanonical interaction with STING and a binding-deficient mutant that retained the tested lysosomal functions without inducing senescence.
- Target / subject
- GNPTAB / STING
- Direction
- Disruption; overexpression; interaction separation
- Cell / setting
- Human mesenchymal progenitor cells
- Boundary
- This is mechanistic human-cell evidence, not treatment of people. Deleting or suppressing GNPTAB everywhere would not follow from an interaction-specific result.
2026-05-19 · India
Immortalized cell line · Cas9 nucleaseAn edit can worsen senescence: TOP2B in HEK293T cells
Researchers at the University of Hyderabad disrupted the TOP2B promoter in HEK293T cells and observed senescence. It is a useful counterexample to the idea that removing gene activity necessarily rejuvenates cells.
- Target / subject
- TOP2B promoter
- Direction
- Promoter deletion
- Cell / setting
- HEK293T cells
- Boundary
- HEK293T is an immortalized laboratory model, not normal aged human tissue. The finding is a directional warning, not a validated human-aging target.
2026-03-28 · China
Cellular experiment · CRISPRaPOLR2A activation: cellular findings are not a checkpoint bypass license
Activating endogenous POLR2A with CRISPRa alleviated senescent phenotypes in the reported system. The assessment describes a pathway connecting LMO7-mediated regulation with MDM4, p53 and p21.
- Target / subject
- LMO7 / POLR2A / MDM4-p53-p21
- Direction
- Activation
- Cell / setting
- Senescence-associated cellular model
- Boundary
- This does not show that broad suppression of protective p53 signaling is a healthy-aging strategy. Specific context, identity and growth safeguards must remain visible.
2026-04-01 · United Kingdom
Single-cell perturbation study · CRISPR screening / single-cell readoutMitoPerturb-Seq: nuclear regulation of mitochondrial outcomes
MitoPerturb-Seq interrogates nuclear genes involved in mitochondrial DNA copy number and heteroplasmy at single-cell resolution. The measured response links nuclear perturbations with mitochondrial state.
- Target / subject
- Nuclear regulators of mitochondrial DNA
- Direction
- Gene-specific perturbation
- Cell / setting
- Single-cell mitochondrial-response models
- Boundary
- The method should not be described as routine direct mitochondrial DNA editing with ordinary Cas9 and a standard guide. Human therapeutic benefit is not established.
2026-10-14 · United States
Cells + animals · cDNA overexpression — not CRISPRSRSF1 is a non-CRISPR finding on the replication watchlist
A cDNA overexpression screen, not CRISPR, identified SRSF1. Reported cellular improvements and small aged-mouse results motivate a replication question.
- Target / subject
- SRSF1
- Direction
- Increased expression
- Cell / setting
- Human fibroblasts and aged mice
- Boundary
- CRISPRa reproduction would be a new hypothesis, not a result of the paper. Small survival cohorts do not establish human lifespan benefit.
Source trail
Scientific summaries are adapted from the supplied 15 October 2026 CRISPR Project Assessment. Source records show the original references and review access; this release is not a new systematic review.
C01 — Yin J, Gao Y, Jing Y, et al. CRISPR screening identifies GNPTAB as a noncanonical STING activator driving cellular senescence. Protein & Cell. 27 July 2026.C03 — Plesa AM, Jung S, Wang HH, et al. Transcriptomic reprogramming screen identifies SRSF1 as a regulator of aging. Nature Aging. 14 October 2026;6:2057–2073.C11 — Saroj N, Velangani HG, Kiran S, Dholaniya PS. Deletion of TOP2B promoter using CRISPR-Cas9 induces senescence in HEK 293T cells. Biochemistry and Biophysics Reports. 19 May 2026;46:102620.C12 — Lai C, Fu W, Liu J, et al. LMO7-mediated POLR2A degradation promotes cellular senescence through the MDM4/p53/p21 axis. Cell Death & Disease. 28 March 2026;17:421.C13 — Burr SP, Auckland K, Glynos A, et al. MitoPerturb-Seq identifies gene-specific single-cell responses to mitochondrial DNA depletion and heteroplasmy. Nature Structural & Molecular Biology. 1 April 2026;33:711–723.Bring one question worth answering.
Tell us the decision, the evidence you have and the gap that blocks the next step. Start with nonconfidential context.