TCIConsultancy
Gene & cell therapy · Vector design · Plasmid CMC

Get the construct right, and everything downstream gets easier.

Independent scientific advisor for AAV, lentiviral and CAR-T programs. I help teams design vectors, plan GMP plasmid supply, build the assays that characterize them, and write the documents that support each phase of development. That includes potency assays for gene-editing therapies delivered by AAV.

Download capabilities statement (PDF)
pTCI-AAV · illustrative transfer plasmid
Experience built at
Vertex PharmaceuticalsAgilent TechnologiesAllerganInvitrogenMyriad ProteomicsProlexys PharmaceuticalsPhD, University of Reading (UK)Inventor of SureVector
Specialty service

Potency assays for gene-editing therapies

Potency is one of the hardest assays to get right for a gene-editing product, and regulators expect a method that reflects how the therapy works. At Vertex I developed a cell-based potency assay for CRISPR editing delivered by AAV. I help teams heading toward IND plan and build theirs.

Talk about your potency assay
  • Potency assay strategy linked to mechanism of action
  • Cell model, readout and reference standard selection
  • Assay development, qualification and phase-appropriate validation plans
  • Supporting transduction, expression and editing-efficiency assays
  • Oversight of potency work at CROs, and transfer to QC
Services

Advice at each stage of the construct lifecycle

From the first sequence design to the documents that support a BLA. Engage me for one stage, carry the program through all four, or bring me in to manage the outside labs doing the work.

1 Design

Vector & construct design

Design reviews and strategy that improve cargo stability, expression and manufacturability before you commit to production.

  • AAV transgene and ITR-containing construct design
  • Lentiviral and CAR-T vector design analysis
  • Codon and sequence optimization, including large cDNAs
  • Helper plasmids and large synthetic assemblies (35–100 kb)
  • Plasmid backbone and barcode strategies
  • Non-viral and alternative cargo delivery approaches
  • CRISPR/Cas editing systems and guide libraries
2 Plasmid

Plasmid & starting-material CMC

Strategy and oversight for the plasmid DNA your AAV or lentiviral process depends on.

  • GMP plasmid sourcing, CDMO selection and campaign oversight
  • Master Cell Bank creation and characterization
  • Manufacturing-grade plasmid specifications and inventory control
  • Planning for in-house plasmid production capability
  • Tech transfer from research to manufacturing
  • Late-stage readiness for plasmid workflows
3 Assays

Analytical & assay development

Characterization and release methods that show your construct and product are what you say they are.

  • NGS verification of plasmids and AAV particles
  • Cell-based potency assays, including for AAV-delivered CRISPR editing
  • Transduction and expression assays
  • PCR, qPCR and LC-MS methods, including residual host-cell DNA
  • Characterization and release assay strategy for AAV and CAR-T
  • Method qualification and transfer to cGMP QC
  • Multiplex PCR and bioanalytical workflows
4 Documents

Sequence analysis & quality documentation

Clear, traceable documents for every phase of development, from early research through BLA.

  • Sequence analysis and construct verification reports
  • SOP authoring and review
  • Cell bank characterization and release documentation
  • Assay qualification packages and risk assessments
  • Drafting and review of regulatory documents, including BLA-stage Type D submissions
  • Support for deviations, investigations and root-cause analysis
+ Across every stage

CRO & CDMO oversight

Most gene and cell therapy work is outsourced. I have spent much of my career managing CROs and CDMOs, and I help you choose the right partners and keep their work on track.

  • Scoping work and preparing requests for proposals
  • Evaluating and selecting CROs and CDMOs
  • Technical oversight of cloning, plasmid and assay projects
  • GMP plasmid and cell bank campaigns at CDMOs
  • Method transfer to and from outside labs
  • Reviewing vendor data, reports and deviations
Signature innovation

Inventor of SureVector

At Agilent I conceived and drove development of SureVector, a modular DNA assembly system in the same class as Gibson assembly, patented as US 10,662,424 B2, Molecular Fabrication. Standardized, pre-validated parts (origins, selection markers, promoters, your gene) join seamlessly in a single reaction, so a lab can go from vector design to finished plasmid in less than a day instead of weeks.

The same thinking runs through my consulting work. A vector should be built from well-understood parts, assembled so it can be verified, and designed with manufacturing in mind.

1 reactionup to 7 fragments assembled seamlessly
< 1 dayfrom design to finished vector
700,000+possible vector configurations

Used to build pooled CRISPR libraries of 60,000+ guides · Braman & Sheffield, 2019

gene of interest promoter selection marker origin expansion part 1 reaction custom vector seamless junctions
Modular parts with overlapping ends → one circular plasmid
Track record

By the numbers

20+years in gene cloning, vector construction and gene therapy
2,000+DNA constructs designed and built over my career
5biotech companies advised on vector design and assay development as a consultant
20–30AAV vectors a month delivered by the team I built at Vertex
100 kblargest synthetic assembly: AAV concatemers for stable production cell lines
60,000+guides in the largest CRISPR genome-editing library I developed
2granted US patents, including the SureVector DNA assembly system
30+analytes in a multiplex PCR assay taken from R&D to manufacturing
IND→BLAregulatory documents drafted and reviewed across all phases
About

Meet Peter

Peter Sheffield, PhD · Founder & Principal Consultant

I have spent more than 20 years designing and building DNA for gene therapy and molecular biology, and leading the teams that do it. At Vertex I built and led the vector construction and plasmid production groups for the AAV research program, delivering 20–30 AAV vectors a month, developing a cell-based potency assay for CRISPR gene editing delivered by AAV, establishing NGS methods for vector QC, and managing GMP plasmid campaigns at CDMOs.

Before that I spent nine years directing synthetic biology and CRISPR R&D at Agilent, where I conceived and led development of the patented SureVector DNA assembly system, and my teams built genome-editing libraries of more than 60,000 guides. Earlier, at Allergan, I worked in biologics CMC, developing release assays and writing GMP documentation for early-phase programs. My career started at Invitrogen, Myriad Proteomics and Prolexys Pharmaceuticals, expressing and purifying proteins for X-ray crystallography.

Since 2024 I have worked as a consultant, first with BioRox, advising five biotech companies on AAV and CAR-T vector design and optimization and on characterization and release assays. I founded TCI Consultancy to continue that work and give gene and cell therapy teams direct access to my experience, without the overhead of building it in-house.

Focus
AAV, lentiviral and CAR-T vectors; plasmid CMC; analytics
Experience
20+ years, discovery through BLA
Training
PhD Molecular Biology, Reading (UK) · BSc Biochemistry & Genetics, Nottingham (UK)
Founder & Principal Consultant · TCI Consultancy
Molecular Biology Consultant, Scientific Advisor · BioRox Inc. · vector design and optimization and assay development for 5 biotech companies
Director, Vector Construction · Vertex Pharmaceuticals
Scientific Program Director, R&D · Agilent Technologies
Senior Scientist, Bioanalytical Method Development · Allergan
Prolexys Pharmaceuticals · Myriad Proteomics · Invitrogen · protein expression and purification for X-ray crystallography
Patents
Molecular Fabrication · the SureVector assembly method and kit: pre-made cassettes with hybridizing ends assembled into plasmids in one reaction
Compositions and methods of producing enterokinase in yeast · yeast expression constructs for recombinant enterokinase production (Allergan, granted 2013)
How I work

Three principles

Design for manufacture

A construct that expresses well in the lab but fails in production costs months. I look at stability, size, ITR integrity and plasmid yield from the first design review.

Verify everything

Every construct, plasmid lot and vector should be confirmed by sequence and by function. I help you put the right NGS and potency methods in place early, so data holds up later.

Document as you go

Traceable records from day one make IND and BLA documentation far easier. I help teams build that habit into their SOPs and workflows.

Expertise

Areas of expertise

Modalities

  • AAV gene therapy
  • Lentiviral vectors
  • CAR-T cell therapy
  • Adenovirus and helper systems
  • CRISPR/Cas gene editing
  • Non-viral delivery
  • Recombinant proteins and biologics
  • Protein expression and purification for structural biology

Construct engineering

  • ITR-containing constructs
  • Codon optimization (e.g. full-length DMD cDNA)
  • Large DNA assembly (35–100 kb)
  • Novel plasmid backbones
  • Barcoding strategies
  • High-throughput cloning

Analytics

  • NGS for plasmid and AAV QC
  • PCR and qPCR, including residual DNA
  • LC-MS
  • Cell-based potency (CRISPR via AAV)
  • Transduction assays
  • Multiplex PCR (30+ analytes)
  • Western blot and activity assays
  • Method qualification

CMC & quality

  • CRO and CDMO selection and oversight
  • GMP plasmid manufacture at CDMOs
  • Master Cell Banks
  • Tech transfer to manufacturing
  • SOPs and GMP documentation
  • Risk assessments
  • Regulatory documents, IND to BLA
Contact

Let's talk about your program

Tell me where your program is and what's in the way. I reply within one to two business days.

peter.sheffield@tci-consultancy.com
Download capabilities statement (PDF)