Meeting report

Scaling the RNA Summit:

Reﬂections

on the 2026 OPT

congress

Paloma H. Giangrande

1,2,3

The Seaport District of Boston, regarded as a

hub

for biotechnology, was more than just

the

venue for the 11th Annual Oligonucleo-

tide,

mRNA,

and Peptide Therapeutics

(OPT)

Congress this week. It served as a

catalyst

for the next generation of nucleic

acid

medicine. In 2026, the perspective

among

hundreds of global scientic leaders

was

clear: the era of “modality isolation”

has

ended, giving way to a new period of

structural and functional convergence in

the

eld.

VOICES FROM THE PLENARY:

DEFINING THE FUTURE

The congress featured a series of impactful

plenary

sessions and keynote addresses

that

connected basic biological science

with

clinical applications. Major highlights

included:

• Timothy

(Boston Children’s Hospi-

tal):

Dr.

Yu’s presentation on personal-

ized

anti-sense

oligonucleotide (ASO)

therapies

outlined how the eld can

rapidly and accurately address ultra-rare

genetic

conditions.

• Brenda

Bass

(University of Utah):

Her

session on double-stranded RNA

(dsRNA)

biology and innate immunity

provided

a foundational understanding

for

developing the next generation of

non-immunogenic

mRNA platforms.

• Debra

Miller

(CureDuchenne): Miller’s

contribution,

representing the patient

perspective,

emphasized that the true

measure

of “emerging modalities” is their

real-world

impact on families dealing

with

rare diseases.

• Mano

Manoharan

(Alnylam Pharma-

ceuticals):

Dr.

Manoharan’s analysis

of the evolution of oligonucleotide

chemistry

emphasized optimizing the

“binder-linker-payload”

architecture to

move

beyond established liver delivery.

highlighted that while lipid nano-

particle

(LNP)

formulations and triva-

lent

GalNAc

(N-Acetylgalactosamine)

conjugation

paved the way for hepatic

success,

the eld is now advancing

into

extrahepatic tissues. This is evi-

denced

the clinical entry of lipid-

conjugated

small interfering RNAs

(siRNAs)

for the CNS and antibody-

conjugated oligonucleotides for muscle

delivery

and blood-brain barrier pene-

tration.

standout

moment was a comprehensive

historical

overview by Laura Sepp-Loren-

zino

(former

Chief Scientic Ofcer [CSO]

Intellia Therapeutics), tracing the devel-

opment

oligonucleotide therapeutics—

from

early chemical modications to cur-

rent

CRISPR

and RNAi technologies. Her

talk

reinforced the persistence needed to

achieve

clinical maturity in the eld. Those

who

missed her session are encouraged to

access

her presentation via the congress por-

tal

for

a complete picture of the eld’s

progress.

EMERGING TECHNOLOGIES: THE

RISE OF RNA EDITING, tRNA, AND

NEXT-GEN MODALITIES

The “mRNA & Emerging Modalities” con-

ference

track

was arguably the most at-

tended,

signaling

a shift in the protagonist

the RNA story. Linear mRNA is no longer

the

sole focus; signicant data was presented

circular RNA (circRNA) platforms,

which

offer enhanced stability, and self-

amplifying

RNA (saRNA), which enables

therapeutic

protein expression at drastically

lower

doses.

This

year,

the scope of “modality” expanded

further

with groundbreaking presentations

on RNA/DNA hybrid oligonucleotides,

RNA

editing, and tRNA therapeutics. Spe-

cically,

discussions

surrounding AIRNA

highlighted

the rapid maturation of

ADAR-mediated

RNA editing, moving the

eld

closer to precise, temporary genetic

corrections

without the risks of permanent

genomic

alteration.

Simultaneously,

the

potential for tRNA to

address

nonsense mutations and protein

misfolding

was underscored by compelling

data

from Tevard and Alltrna. These presen-

tations

illustrated

how tRNA-based medi-

cines

could

potentially treat a vast array of

genetic

diseases by “xing” the translational

process

itself.

Discussions

led

by industry experts like

Dmitry

Samarsky (ARNAgen) and Wuming

Yan

(Asymchem) further highlighted that

the

“delivery constraint” for these diverse

molecules

is being solved through AI-assis-

ted

lipid

design and ligand-conjugation

strategies.

BEYOND THE LIVER: THE

EXTRAHEPATIC FRONTIER

A major theme throughout the congress was

the

advancement toward extrahepatic deliv-

ery.

While LNPs have traditionally targeted

the

liver, this year’s sessions highlighted suc-

cessful

AI-driven

lipid designs enabling de-

livery

the central nervous system, muscle,

and

heart. Dan Peer (Tel Aviv University)

presented

notable work on modular delivery

platforms

that can reach leukocytes and

other

previously inaccessible cell types,

pushing

the boundaries of systemic RNA

administration.

CMC TRACK HIGHLIGHTS:

SCALING INNOVATION

The Chemistry, Manufacturing, and

Controls

(CMC) sessions at this year’s

OPT

Congress signaled a denitive shift

Program Therapeutics, Inc, Belmont, MA 02478,

USA;

Biologic Insights, LLC, Belmont, MA 02478,

USA;

Molecular Therapy - Nucleic Acids,

Belmont, MA 02478, USA

Correspondence:

Paloma

H. Giangrande, Program

Therapeutics, Inc.

E-mail:

phgiangrande@gmail.com

Published

by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.

This

is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

from “bespoke” laboratory synthesis

toward

a standardized industrial frame-

work.

The

discussions centered on three

critical

pillars for the next generation of

therapeutics.

• Managing

Molecular

Complexity: A ma-

jor

focus

was placed on the analytical chal-

lenges

peptide-oligonucleotide conju-

gates

and

circRNA. Experts emphasized

using

long-read sequencing and mass

photometry

to ensure product purity, as

the

industry moves toward diverse extra-

hepatic

targets.

• Sustainable

Manufacturing: The track

highlighted

a “green” revolution, show-

casing

continuous

chromatography and

enzymatic

synthesis as essential tools to

reduce

the massive solvent waste tradition-

ally

associated

with solid-phase synthesis.

• Good

Manufacturing

Practice Readi-

ness:

The

consensus was clear—the pri-

mary

hurdle

has shifted from discovery

scalability. Bridging the gap between

innovative

RNA modalities and robust,

global-scale

production is now the indus-

try’s

most

urgent mandate.

CLOSING THOUGHTS: THE MTNA

MISSION

The technologies showcased this week—

from

RNA editing to radioligand peptide

conjugates—exemplify

the high-impact

research

that Molecular Therapy – Nucleic

Acids

aims to publish. The congress

conrmed

that the eld is moving toward

precision

medicine on a broad scale.

Reecting

the insights from Boston, it is

evident

that the transition from “innovative

science”

to “transformative medicine” is

already

underway in both laboratory and

clinical

settings.

DECLARATION OF INTERESTS

P Giangrande owns stock/shares in Wave Life Sciences

and

is the Founder and CSO of Program Therapeutics,

Inc., a biotechnology company focused on RNA

therapeutics.

www.moleculartherapy.org

Meeting report

2 Molecular Therapy: Nucleic Acids Vol. 37 June 2026